Pub Date : 2024-08-26DOI: 10.2174/0115748928293003240817180839
Duheyi Zhang, Lianxi Mai, Lizao Zhang, Guoxin Huang, Zhaoyu Lin, Shuang Wang, Guangxin Rao, Shule Xie, Chaobin Pan
Introduction: N6-methyladenosine (m6A) modifications of RNAs are associated with many cancer types. Nevertheless, the function of the m6A reader IGF2BP2 in oral squamous cell carcinoma (OSCC) has yet to be ascertained.
Aims: The objective of this investigation was to elucidate the role of IGF2BP2 in OSCC and delineate the associated mechanisms.
Method: Elevated expression of IGF2BP2 was observed in OSCC, and this overexpression significantly correlated with adverse prognostic outcomes in patients with OSCC. In vitro analyses demonstrated that silencing of IGF2BP2 attenuated the proliferation, migration, and invasion capabilities of oral cancer cells while concurrently promoting apoptosis.
Results: In vivo experiments demonstrated that IGF2BP2 promoted OSCC growth. RNA-seq and m6A-seq were utilized to elucidate the downstream targets of IGF2BP2. Through bioinformatic analysis, we identified the long noncoding RNA (lncRNA) UCA1 as a target. IGF2BP2 was found to maintain the stability of UCA1 in an m6A-dependent manner by binding to m6A-modified UCA1 and plays an oncogenic role in OSCC through UCA1.
Conclusion: In conclusion, we identified IGF2BP2 as a prognostic biomarker of OSCC, and the IGF2BP2-UCA1 axis was found to promote OSCC progression and may perform as a novel therapeutic target.
{"title":"The m6A Reader IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression by Maintaining UCA1 Stability.","authors":"Duheyi Zhang, Lianxi Mai, Lizao Zhang, Guoxin Huang, Zhaoyu Lin, Shuang Wang, Guangxin Rao, Shule Xie, Chaobin Pan","doi":"10.2174/0115748928293003240817180839","DOIUrl":"https://doi.org/10.2174/0115748928293003240817180839","url":null,"abstract":"<p><strong>Introduction: </strong>N6-methyladenosine (m6A) modifications of RNAs are associated with many cancer types. Nevertheless, the function of the m6A reader IGF2BP2 in oral squamous cell carcinoma (OSCC) has yet to be ascertained.</p><p><strong>Aims: </strong>The objective of this investigation was to elucidate the role of IGF2BP2 in OSCC and delineate the associated mechanisms.</p><p><strong>Method: </strong>Elevated expression of IGF2BP2 was observed in OSCC, and this overexpression significantly correlated with adverse prognostic outcomes in patients with OSCC. In vitro analyses demonstrated that silencing of IGF2BP2 attenuated the proliferation, migration, and invasion capabilities of oral cancer cells while concurrently promoting apoptosis.</p><p><strong>Results: </strong>In vivo experiments demonstrated that IGF2BP2 promoted OSCC growth. RNA-seq and m6A-seq were utilized to elucidate the downstream targets of IGF2BP2. Through bioinformatic analysis, we identified the long noncoding RNA (lncRNA) UCA1 as a target. IGF2BP2 was found to maintain the stability of UCA1 in an m6A-dependent manner by binding to m6A-modified UCA1 and plays an oncogenic role in OSCC through UCA1.</p><p><strong>Conclusion: </strong>In conclusion, we identified IGF2BP2 as a prognostic biomarker of OSCC, and the IGF2BP2-UCA1 axis was found to promote OSCC progression and may perform as a novel therapeutic target.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The precise function of Tolloid Like 2 (TLL2) remains uncertain within the context of Lung Adenocarcinoma (LUAD).
Objective: The primary objective of this investigation was to conduct a thorough analysis.
Methods: To assess its diagnostic utility, data from The Cancer Genome Atlas (TCGA) database were used to assess TLL2 expression in pan-cancer and LUAD. The study has also investigated the correlation between TLL2 expression levels and LUAD symptoms and prognosis. Furthermore, the study has explored possible regulatory networks involving TLL2, including its association with immune infiltration, tumor stemness index (mRNAsi), and drug sensitivity in LUAD. We have explored TLL2 expression in single-cell sequencing of LUAD and the genomic variation and clinical significance of TLL2 in LUAD. The expression of TLL2 has been validated in GSE87340 and cell lines by quantitative Real-time PCR (qRT-PCR).
Results: An abnormal expression of TLL2 has been found in pan-cancer and LUAD. In LUAD patients, elevated levels of TLL2 were significantly related to the T stage (p = 0.046) and the pathological stage (p = 0.016). The expression of TLL2 in patients with LUAD was significantly associated with poorer Overall Survival (OS) (p < 0.001). The expression of TLL2 was determined to be an independent predictor of poorer OS (p = 0.042). TLL2 was associated with ribosome, neuroactive ligand-receptor interaction, allograft rejection, ECM receptor interaction, asthma, porphyrin and chlorophyll metabolism, focal adhesion, pentose and glucuronate inter-conversions, and ascorbate and aldarate metabolism. The expression of TLL2 in LUAD was correlated with immune infiltration and mRNAsi. The expression of TLL2 was significantly and negatively correlated with TAK-715, XMD13-2, STF-62247, OSI-930, and EHT-1864 in LUAD. The TLL2 gene was up- -regulated in multiple individual LUAD cells. LUAD patients with altered TLL2 had a shorter PFS as opposed to those with unaltered TLL2. The expression of TLL2 was significantly increased in LUAD cells.
Conclusion: For patients with LUAD, TLL2 may serve as an immunotherapeutic target and a useful prognosis biomarker.
{"title":"Comprehensive Analysis and Experimental Validation of TLL2 as a Potential New Prognostic Biomarker Associated with Immune Infiltration in Lung Adenocarcinoma.","authors":"Jing Jiang, Zhongye Du, Haijuan Tang, Yingying Huang, Dongbing Li, Qiuli Liang","doi":"10.2174/0115748928303392240817131807","DOIUrl":"https://doi.org/10.2174/0115748928303392240817131807","url":null,"abstract":"<p><strong>Background: </strong>The precise function of Tolloid Like 2 (TLL2) remains uncertain within the context of Lung Adenocarcinoma (LUAD).</p><p><strong>Objective: </strong>The primary objective of this investigation was to conduct a thorough analysis.</p><p><strong>Methods: </strong>To assess its diagnostic utility, data from The Cancer Genome Atlas (TCGA) database were used to assess TLL2 expression in pan-cancer and LUAD. The study has also investigated the correlation between TLL2 expression levels and LUAD symptoms and prognosis. Furthermore, the study has explored possible regulatory networks involving TLL2, including its association with immune infiltration, tumor stemness index (mRNAsi), and drug sensitivity in LUAD. We have explored TLL2 expression in single-cell sequencing of LUAD and the genomic variation and clinical significance of TLL2 in LUAD. The expression of TLL2 has been validated in GSE87340 and cell lines by quantitative Real-time PCR (qRT-PCR).</p><p><strong>Results: </strong>An abnormal expression of TLL2 has been found in pan-cancer and LUAD. In LUAD patients, elevated levels of TLL2 were significantly related to the T stage (p = 0.046) and the pathological stage (p = 0.016). The expression of TLL2 in patients with LUAD was significantly associated with poorer Overall Survival (OS) (p < 0.001). The expression of TLL2 was determined to be an independent predictor of poorer OS (p = 0.042). TLL2 was associated with ribosome, neuroactive ligand-receptor interaction, allograft rejection, ECM receptor interaction, asthma, porphyrin and chlorophyll metabolism, focal adhesion, pentose and glucuronate inter-conversions, and ascorbate and aldarate metabolism. The expression of TLL2 in LUAD was correlated with immune infiltration and mRNAsi. The expression of TLL2 was significantly and negatively correlated with TAK-715, XMD13-2, STF-62247, OSI-930, and EHT-1864 in LUAD. The TLL2 gene was up- -regulated in multiple individual LUAD cells. LUAD patients with altered TLL2 had a shorter PFS as opposed to those with unaltered TLL2. The expression of TLL2 was significantly increased in LUAD cells.</p><p><strong>Conclusion: </strong>For patients with LUAD, TLL2 may serve as an immunotherapeutic target and a useful prognosis biomarker.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.2174/0115748928321372240813080131
Ali Raza Ishaq, Tahira Younis, Shankun Lin, Muhammad Usman, Tingfang Wang, Zhe-Sheng Chen
Tumor cells have distorted enzymatic houses, which change the metabolic state from oxidative phosphorylation to glycolysis with high lactate levels in a hypoxic environment. Redrafting the metabolic profile is an emerging hallmark of cancer. Glycolytic enzyme amplification occurs in about 70% of all malignancies. Current studies have found that PFK-1 overexpression is linked to cell migration, proliferation, and Overall Survival (OS) rate in various human cancer cell lines. This review intended to uncover the bona fide therapeutic target for cancer therapy and elucidate the role of PFK-1 in cancer. Furthermore, this review has outlined the listed pharmacological and genetic inhibitors of PFK-1. Following this review, future studies on PFK-1 should emphasize the molecular pathways implicated in PFK-1 overexpression in cancer development. The terms "PFK-1", "PFKP-1", "PFKL-1", "PFKM-1", "PFKM-1 and cancer", "PFKP-1 and cancer", "PFKL-1 and cancer", and "inhibitors of PFK-1" were used to retrieve the information from a variety of databases, including PubMed, Scopus, Google Scholar, and ScienceDirect. In a variety of malignancies, inhibiting the expression of PFK-1 isoforms has been reported to be the most effective therapeutic method. Overexpression of PFK-1 isoforms induces the Warburg effect, cell proliferation, and carcinogenesis by downregulating apoptotic proteins, such as active caspase-3, caspase-9, and caspase-8. YY1, synoviolin, Sh-RNA-507, SNAI, miR-520a/b/e, miR-128, and β-miR-6517 are some of the putative genetic inhibitors against PFK-1 that have been used to manage the development of malignancies. Pharmacological inhibitors, such as penfluridol, synoviolin/HRD1, quercetin, ginsenoside 20(S)-Rg3, triptolide, worenine, acetylsalicylic acid, and salicylic acid, can regulate the advancement of malignancies by inhibiting PFK-1. Thus, PFK-1 is a promising molecular biomarker for cancer treatment. A prospective investigation can validate the unbiased approaches for discovering brandnew PFK-1 inhibitors for cancer treatment.
{"title":"Phosphofructokinase-1 in Cancer: A Promising Target for Diagnosis and Therapy.","authors":"Ali Raza Ishaq, Tahira Younis, Shankun Lin, Muhammad Usman, Tingfang Wang, Zhe-Sheng Chen","doi":"10.2174/0115748928321372240813080131","DOIUrl":"https://doi.org/10.2174/0115748928321372240813080131","url":null,"abstract":"<p><p>Tumor cells have distorted enzymatic houses, which change the metabolic state from oxidative phosphorylation to glycolysis with high lactate levels in a hypoxic environment. Redrafting the metabolic profile is an emerging hallmark of cancer. Glycolytic enzyme amplification occurs in about 70% of all malignancies. Current studies have found that PFK-1 overexpression is linked to cell migration, proliferation, and Overall Survival (OS) rate in various human cancer cell lines. This review intended to uncover the bona fide therapeutic target for cancer therapy and elucidate the role of PFK-1 in cancer. Furthermore, this review has outlined the listed pharmacological and genetic inhibitors of PFK-1. Following this review, future studies on PFK-1 should emphasize the molecular pathways implicated in PFK-1 overexpression in cancer development. The terms \"PFK-1\", \"PFKP-1\", \"PFKL-1\", \"PFKM-1\", \"PFKM-1 and cancer\", \"PFKP-1 and cancer\", \"PFKL-1 and cancer\", and \"inhibitors of PFK-1\" were used to retrieve the information from a variety of databases, including PubMed, Scopus, Google Scholar, and ScienceDirect. In a variety of malignancies, inhibiting the expression of PFK-1 isoforms has been reported to be the most effective therapeutic method. Overexpression of PFK-1 isoforms induces the Warburg effect, cell proliferation, and carcinogenesis by downregulating apoptotic proteins, such as active caspase-3, caspase-9, and caspase-8. YY1, synoviolin, Sh-RNA-507, SNAI, miR-520a/b/e, miR-128, and β-miR-6517 are some of the putative genetic inhibitors against PFK-1 that have been used to manage the development of malignancies. Pharmacological inhibitors, such as penfluridol, synoviolin/HRD1, quercetin, ginsenoside 20(S)-Rg3, triptolide, worenine, acetylsalicylic acid, and salicylic acid, can regulate the advancement of malignancies by inhibiting PFK-1. Thus, PFK-1 is a promising molecular biomarker for cancer treatment. A prospective investigation can validate the unbiased approaches for discovering brandnew PFK-1 inhibitors for cancer treatment.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20DOI: 10.2174/0115748928332384240812060751
Yue Wu, Li Rong, Suifeng Zhang, Yuxi He, Na Song, Guoqing Zuo, Zhechuan Mei
Background: Angelica sinensis (Oliv.) Diels, a renowned traditional Chinese medicine, has gained widespread recognition for its antitumor properties. Further investigation is warranted to determine whether ligustilide (LIG), which is extracted from this plant, can effectively inhibit tumors.
Objective: We delved into the impact of LIG on cholangiocarcinoma cells, aiming to unravel the mechanisms underlying its effects.
Materials and methods: Cholangiocarcinoma cells (HuccT1 and RBE) were exposed to varying concentrations of LIG (2, 5, 10, 15, 20 μg/mL) for 24, 48, and 72 h. After identifying differentially expressed genes, stable transcription strains were utilized to explore LIG's antitumor mechanism. The inhibitory effects of LIG (5 μg/mL, 48 h) were assessed by CCK-8, colony formation, wound healing, transwell migration, western blotting, and immunofluorescence. In vivo, experiments in NOG mice (Ac, Ac+LIG; five per group) evaluated LIG's antiproliferative efficacy (5 mg/kg, intraperitoneal injection, 18-day period).
Results: LIG significantly inhibited cell proliferation and migration with IC50 5.08 and 5.77 μg/mL in HuccT1 and RBE cell lines at 48h, increased the expression of E-cadherin while decreased N-cadherin and the protein of PI3K/AKT pathway. Silenced NDRG1 (N-Myc downstream- regulated gene 1) attenuated these effects. In vivo, the AC+LIG group (LIG, 5 mg/kg, qd, 18 d) exhibited smaller tumor volumes compared to the Ac group. The expression of Ki-67 was significantly downregulated in the AC+LIG group.
Conclusion: For the first time, our study has revealed that LIG holds therapeutic potential for treating cholangiocarcinoma. These findings hold promise for advancing innovative therapeutic approaches in the treatment of cholangiocarcinoma. LIG may serve as a useful patent for treating CCA.
背景:当归(Oliv. Diels)是一种著名的传统中药,其抗肿瘤特性已得到广泛认可。从这种植物中提取的藁本内酯(LIG)是否能有效抑制肿瘤,还有待进一步研究:我们深入研究了藁本内酯对胆管癌细胞的影响,旨在揭示其作用机制:将胆管癌细胞(HuccT1和RBE)暴露于不同浓度的LIG(2、5、10、15、20 μg/mL)中24、48和72小时。LIG(5 μg/mL,48 小时)的抑制作用通过 CCK-8、菌落形成、伤口愈合、Transwell 迁移、Western 印迹和免疫荧光进行评估。在 NOG 小鼠(Ac、Ac+LIG;每组 5 只)体内进行的实验评估了 LIG 的抗增殖功效(5 毫克/千克,腹腔注射,18 天):48小时后,LIG能明显抑制HuccT1和RBE细胞株的增殖和迁移,IC50分别为5.08和5.77 μg/mL,并能增加E-cadherin的表达,同时降低N-cadherin和PI3K/AKT通路蛋白的表达。抑制 NDRG1(N-Myc 下游调控基因 1)可减轻这些影响。在体内,AC+LIG 组(LIG,5 mg/kg,qd,18 d)的肿瘤体积比 Ac 组小。AC+LIG组的Ki-67表达明显下调:我们的研究首次揭示了 LIG 治疗胆管癌的潜力。这些发现有望推动胆管癌治疗方法的创新。LIG 可作为治疗 CCA 的有效专利。
{"title":"Ligustilide Inhibits the PI3K/AKT Signalling Pathway and Suppresses Cholangiocarcinoma Cell Proliferation, Migration, and Invasion.","authors":"Yue Wu, Li Rong, Suifeng Zhang, Yuxi He, Na Song, Guoqing Zuo, Zhechuan Mei","doi":"10.2174/0115748928332384240812060751","DOIUrl":"https://doi.org/10.2174/0115748928332384240812060751","url":null,"abstract":"<p><strong>Background: </strong>Angelica sinensis (Oliv.) Diels, a renowned traditional Chinese medicine, has gained widespread recognition for its antitumor properties. Further investigation is warranted to determine whether ligustilide (LIG), which is extracted from this plant, can effectively inhibit tumors.</p><p><strong>Objective: </strong>We delved into the impact of LIG on cholangiocarcinoma cells, aiming to unravel the mechanisms underlying its effects.</p><p><strong>Materials and methods: </strong>Cholangiocarcinoma cells (HuccT1 and RBE) were exposed to varying concentrations of LIG (2, 5, 10, 15, 20 μg/mL) for 24, 48, and 72 h. After identifying differentially expressed genes, stable transcription strains were utilized to explore LIG's antitumor mechanism. The inhibitory effects of LIG (5 μg/mL, 48 h) were assessed by CCK-8, colony formation, wound healing, transwell migration, western blotting, and immunofluorescence. In vivo, experiments in NOG mice (Ac, Ac+LIG; five per group) evaluated LIG's antiproliferative efficacy (5 mg/kg, intraperitoneal injection, 18-day period).</p><p><strong>Results: </strong>LIG significantly inhibited cell proliferation and migration with IC50 5.08 and 5.77 μg/mL in HuccT1 and RBE cell lines at 48h, increased the expression of E-cadherin while decreased N-cadherin and the protein of PI3K/AKT pathway. Silenced NDRG1 (N-Myc downstream- regulated gene 1) attenuated these effects. In vivo, the AC+LIG group (LIG, 5 mg/kg, qd, 18 d) exhibited smaller tumor volumes compared to the Ac group. The expression of Ki-67 was significantly downregulated in the AC+LIG group.</p><p><strong>Conclusion: </strong>For the first time, our study has revealed that LIG holds therapeutic potential for treating cholangiocarcinoma. These findings hold promise for advancing innovative therapeutic approaches in the treatment of cholangiocarcinoma. LIG may serve as a useful patent for treating CCA.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.2174/0115748928320508240802055846
Zhi-Jie Yu, Shun-Wen Guo, Bi-Shu Wang, Shi Ouyang, Xian-Huan Zhang, Zi-Zhuo Zhao, Jin-Quan Wang
Background: Radiofrequency ablation (RFA) is an effective therapy for hepatocellular carcinoma (HCC). However, incomplete radiofrequency ablation (IRFA) can promote the progression of residual cancer cells, which is a serious problem in the clinical application of RFA. Therefore, it is of great significance to explore the mechanism and countermeasures of the progression of residual tumors after IRFA. Our previous study confirmed that IRFA can activate the hypoxia/ autophagy pathway of residual tumors in mice and then induce the proliferation of residual tumor cells. Additionally, we found a metal ruthenium complex [Ru(bpy)2(ipad)](ClO4)2 (Ru, where bpy = 2,2'-bipyridine and ipad = 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline) can effectively inhibit hypoxia-inducible factor (HIF-1α) and has good anti-tumor effect in a hypoxic environment; however, whether Ru could suppress the proliferation of residual tumor cells after IRFA is unknown.
Objective: This study intends to evaluate the effect of Ru in suppressing the proliferation of residual hepatocellular carcinoma after IRFA in a mice model.
Methods: The Hepa1-6 xenograft mouse model was established in C57BL/6 mice to simulate clinical IRFA. H&E staining was used to evaluate the biosafety of major organs in the treated mice. TUNEL assay was employed to assess the antitumor effect. Immunohistochemically and immunofluorescence staining was performed to detect the expression of HIF-1α and autophagy-related proteins. The ELISA assay was used to examine the cytokines of interferon-gamma (IFN-γ) and interleukin 10 (IL-10).
Results: Our findings revealed that the residual tumor relapsed via the HIF-1α/LC3B/P62 autophagy- related pathway after IRFA, while Ru could suppress this process. In addition, it was demonstrated that Ru could effectively activate the immune system of the mice and reverse the tumor immune suppression microenvironment after IRFA.
Conclusion: The ruthenium complex Ru could suppress the proliferation of residual hepatocellular carcinoma cells after IRFA in the mice model. This study introduces a novel approach that combines the use of ruthenium complexes with IRFA, offering a potential solution to address the reoccurrence of residual liver cancer following IRFA in clinical settings.
{"title":"Ruthenium Complex Suppresses Proliferation of Residual Hepatocellular Carcinoma after Incomplete Radiofrequency Ablation Therapy.","authors":"Zhi-Jie Yu, Shun-Wen Guo, Bi-Shu Wang, Shi Ouyang, Xian-Huan Zhang, Zi-Zhuo Zhao, Jin-Quan Wang","doi":"10.2174/0115748928320508240802055846","DOIUrl":"https://doi.org/10.2174/0115748928320508240802055846","url":null,"abstract":"<p><strong>Background: </strong>Radiofrequency ablation (RFA) is an effective therapy for hepatocellular carcinoma (HCC). However, incomplete radiofrequency ablation (IRFA) can promote the progression of residual cancer cells, which is a serious problem in the clinical application of RFA. Therefore, it is of great significance to explore the mechanism and countermeasures of the progression of residual tumors after IRFA. Our previous study confirmed that IRFA can activate the hypoxia/ autophagy pathway of residual tumors in mice and then induce the proliferation of residual tumor cells. Additionally, we found a metal ruthenium complex [Ru(bpy)2(ipad)](ClO4)2 (Ru, where bpy = 2,2'-bipyridine and ipad = 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline) can effectively inhibit hypoxia-inducible factor (HIF-1α) and has good anti-tumor effect in a hypoxic environment; however, whether Ru could suppress the proliferation of residual tumor cells after IRFA is unknown.</p><p><strong>Objective: </strong>This study intends to evaluate the effect of Ru in suppressing the proliferation of residual hepatocellular carcinoma after IRFA in a mice model.</p><p><strong>Methods: </strong>The Hepa1-6 xenograft mouse model was established in C57BL/6 mice to simulate clinical IRFA. H&E staining was used to evaluate the biosafety of major organs in the treated mice. TUNEL assay was employed to assess the antitumor effect. Immunohistochemically and immunofluorescence staining was performed to detect the expression of HIF-1α and autophagy-related proteins. The ELISA assay was used to examine the cytokines of interferon-gamma (IFN-γ) and interleukin 10 (IL-10).</p><p><strong>Results: </strong>Our findings revealed that the residual tumor relapsed via the HIF-1α/LC3B/P62 autophagy- related pathway after IRFA, while Ru could suppress this process. In addition, it was demonstrated that Ru could effectively activate the immune system of the mice and reverse the tumor immune suppression microenvironment after IRFA.</p><p><strong>Conclusion: </strong>The ruthenium complex Ru could suppress the proliferation of residual hepatocellular carcinoma cells after IRFA in the mice model. This study introduces a novel approach that combines the use of ruthenium complexes with IRFA, offering a potential solution to address the reoccurrence of residual liver cancer following IRFA in clinical settings.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-18DOI: 10.2174/0115748928297769240611055258
Juan Yang, Chengli Wen, Ping Li, Mingxiao Yao, Jing Wang
Background: Ovarian cancer is one of the most common gynecological malignancies globally, and immunotherapy has emerged as a promising treatment strategy in recent years. However, the effectiveness of immunotherapy is often limited by immune escape mechanisms.
Objective: To unravel the immune response mechanisms in ovarian cancer, this study aimed to employ integrated Weighted Gene Co-expression Network Analysis (WGCNA), machine learning, and single-- cell sequencing analysis to systematically investigate immune infiltration-related molecular features in ovarian cancer patients and experimentally validate the molecular mechanisms of the immune response. This research may provide a new theoretical foundation and treatment strategy for immune-based therapies in ovarian cancer.
Methods: Relevant ovarian cancer datasets were collected from public databases. The ConsensusCluster- Plus and ggplot2 R packages were used to perform dimensionality reduction and clustering analysis of immune infiltration-related genes. Various algorithms were employed to select the best ovarian cancer prognostic model with OC consistency. The prognostic value of angiogenesis and immune-related gene expression was evaluated through Kaplan-Meier survival analysis, and the impact of immune infiltration on immune function in ovarian cancer patients was assessed. Functional pathways were identified using the Gene Set Enrichment Analysis (GSEA) method, and the infiltration abundance of immune and stromal components was inferred using the single-sample Gene Set Enrichment Analysis (ssGSEA) method. The influence of angiogenesis on the cellular level of Ovarian Cancer (OC) was explored in single- cell sequencing data, followed by in vitro cell experiments for further validation. The effect of the angiogenesis model on OC was evaluated through the above-mentioned research and experiments, aiming to investigate the mechanism of targeted therapy strategies in ovarian cancer.
Results: Immune-related data were collected from ovarian cancer patients in this study. Through WGCNA analysis, the MEturquoise module was identified, and a total of 1018 hub genes were determined. A prediction model was constructed using machine learning, with CoxBoost+StepCox selected as the best model, leading to the identification of 10 genes associated with ovarian cancer. Patients with high AIDPS had shorter survival time, and GSEA analysis revealed enrichment in immune-related pathways. Single-sample gene set enrichment analysis demonstrated increased immune cell infiltration and malignant stromal changes in the high AIDPS group. Results from in vitro cell experiments showed that silencing RPL31 inhibited the proliferation and migration of ovarian cancer cells while enhancing immune response capability.
Conclusion: AIDPS holds significant clinical significance in Ovarian Cancer (OC) with poor progn
背景:卵巢癌是全球最常见的妇科恶性肿瘤之一:卵巢癌是全球最常见的妇科恶性肿瘤之一,近年来,免疫疗法已成为一种前景广阔的治疗策略。然而,免疫疗法的有效性往往受到免疫逃逸机制的限制:为揭示卵巢癌的免疫应答机制,本研究旨在综合运用加权基因共表达网络分析(WGCNA)、机器学习和单细胞测序分析等方法,系统研究卵巢癌患者免疫浸润相关的分子特征,并通过实验验证免疫应答的分子机制。这项研究可为卵巢癌的免疫疗法提供新的理论基础和治疗策略:方法:从公共数据库中收集相关的卵巢癌数据集。使用 ConsensusCluster- Plus 和 ggplot2 R 软件包对免疫浸润相关基因进行降维和聚类分析。研究人员采用了多种算法来选择具有 OC 一致性的最佳卵巢癌预后模型。通过 Kaplan-Meier 生存分析评估了血管生成和免疫相关基因表达的预后价值,并评估了免疫浸润对卵巢癌患者免疫功能的影响。利用基因组富集分析(Gene Set Enrichment Analysis,GSEA)方法确定了功能通路,并利用单样本基因组富集分析(ssGSEA)方法推断了免疫和基质成分的浸润丰度。在单细胞测序数据中探讨了血管生成对卵巢癌(OC)细胞水平的影响,然后进行体外细胞实验进一步验证。通过上述研究和实验,评估了血管生成模型对卵巢癌的影响,旨在研究卵巢癌靶向治疗策略的机制:本研究收集了卵巢癌患者的免疫相关数据。通过WGCNA分析,确定了MEturquoise模块,并确定了1018个枢纽基因。利用机器学习构建了一个预测模型,其中CoxBoost+StepCox被选为最佳模型,从而确定了10个与卵巢癌相关的基因。高AIDPS患者的生存时间较短,GSEA分析显示了免疫相关通路的富集。单样本基因组富集分析显示,高AIDPS组的免疫细胞浸润和恶性基质变化增加。体外细胞实验结果显示,沉默 RPL31 可抑制卵巢癌细胞的增殖和迁移,同时增强免疫反应能力:结论:AIDPS 在卵巢癌(OC)中具有重要的临床意义,高 AIDPS 患者的预后较差。这些患者表现出更明显的基因组变异、更密集的免疫细胞浸润以及对免疫疗法更强的耐受性。重要的是,抑制 AIDPS 的关键成分 RPL31 的表达可以显著抑制卵巢癌细胞的增殖、迁移和侵袭性,同时刺激效应 T 细胞的细胞毒性并促进免疫反应,从而减缓卵巢癌的进展。
{"title":"Identification of Immune Infiltration-related Molecular Features in Ovarian Cancer Patients and Experimental Validation of Immune Response Molecular Mechanisms through Integrated WGCNA, Machine Learning, and Single-cell Sequencing Analysis.","authors":"Juan Yang, Chengli Wen, Ping Li, Mingxiao Yao, Jing Wang","doi":"10.2174/0115748928297769240611055258","DOIUrl":"https://doi.org/10.2174/0115748928297769240611055258","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is one of the most common gynecological malignancies globally, and immunotherapy has emerged as a promising treatment strategy in recent years. However, the effectiveness of immunotherapy is often limited by immune escape mechanisms.</p><p><strong>Objective: </strong>To unravel the immune response mechanisms in ovarian cancer, this study aimed to employ integrated Weighted Gene Co-expression Network Analysis (WGCNA), machine learning, and single-- cell sequencing analysis to systematically investigate immune infiltration-related molecular features in ovarian cancer patients and experimentally validate the molecular mechanisms of the immune response. This research may provide a new theoretical foundation and treatment strategy for immune-based therapies in ovarian cancer.</p><p><strong>Methods: </strong>Relevant ovarian cancer datasets were collected from public databases. The ConsensusCluster- Plus and ggplot2 R packages were used to perform dimensionality reduction and clustering analysis of immune infiltration-related genes. Various algorithms were employed to select the best ovarian cancer prognostic model with OC consistency. The prognostic value of angiogenesis and immune-related gene expression was evaluated through Kaplan-Meier survival analysis, and the impact of immune infiltration on immune function in ovarian cancer patients was assessed. Functional pathways were identified using the Gene Set Enrichment Analysis (GSEA) method, and the infiltration abundance of immune and stromal components was inferred using the single-sample Gene Set Enrichment Analysis (ssGSEA) method. The influence of angiogenesis on the cellular level of Ovarian Cancer (OC) was explored in single- cell sequencing data, followed by in vitro cell experiments for further validation. The effect of the angiogenesis model on OC was evaluated through the above-mentioned research and experiments, aiming to investigate the mechanism of targeted therapy strategies in ovarian cancer.</p><p><strong>Results: </strong>Immune-related data were collected from ovarian cancer patients in this study. Through WGCNA analysis, the MEturquoise module was identified, and a total of 1018 hub genes were determined. A prediction model was constructed using machine learning, with CoxBoost+StepCox selected as the best model, leading to the identification of 10 genes associated with ovarian cancer. Patients with high AIDPS had shorter survival time, and GSEA analysis revealed enrichment in immune-related pathways. Single-sample gene set enrichment analysis demonstrated increased immune cell infiltration and malignant stromal changes in the high AIDPS group. Results from in vitro cell experiments showed that silencing RPL31 inhibited the proliferation and migration of ovarian cancer cells while enhancing immune response capability.</p><p><strong>Conclusion: </strong>AIDPS holds significant clinical significance in Ovarian Cancer (OC) with poor progn","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-11DOI: 10.2174/0115748928282936240530105434
Xiaomei Meng, Dong You, Ruizhen Ren
Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn.
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Bentham science disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
{"title":"Withdrawn: Fumarate-1 Mediates the Regulation of Mitochondrial Homeostasis by PGC-1α to Promote Cell Pyroptosis and Inhibit the Thyroid Cancer","authors":"Xiaomei Meng, Dong You, Ruizhen Ren","doi":"10.2174/0115748928282936240530105434","DOIUrl":"10.2174/0115748928282936240530105434","url":null,"abstract":"<p><p>Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn.</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php.</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-11DOI: 10.2174/0115748928265981231204044653
Siqi Wang, Fang Ji, Xiaoli Gao, Zhiyi Li, Si Lv, Juan Zhang, Jiarui Luo, Dan Li, Jie Yan, Huayang Zhang, Kaicheng Fang, Lin Wu, Miaoling Li
Background: Lenvatinib is a tyrosine kinase inhibitor that can improve progression-free survival in patients with thyroid cancer and hepatocellular carcinoma. However, it is limited by adverse cardiovascular events, including hypertension and cardiac dysfunction. Activation of endoplasmic reticulum stress is involved in cardiomyocyte apoptosis.
Objective: This study aimed to confirm whether the cardiotoxicity of lenvatinib is associated with endoplasmic reticulum stress by targeting the activating transcription factor 6 (ATF6), inositol- requiring enzyme 1α (IRE1α) and protein kinase RNA-like ER kinase (PERK) signaling pathways.
Methods: Male C57/BL6 mice were intragastric administration with 30 mg/kg/day lenvatinib. Electrocardiography (ECG) and echocardiography were used to detect arrhythmias and cardiac function. Neonatal rat cardiomyocytes were treated with lenvatinib for 48h. Cell counting kit (CCK8), 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFHDA), Hoechst 33258 and dihydrorhodamine 123 were respectively used for evaluating cell viability, the level of reactive oxygen species (ROS), nuclear morphological changes and mitochondrial membrane potential (MMP) level.
Results: Lenvatinib remarkably decreased the posterior wall thickness of left ventricle during diastole and systole but caused little decrease to the left ventricular ejection fraction (LVEF, %). Furthermore, lenvatinib greatly prolonged the corrected QT interval (QTc) and altered the morphology of cardiomyocytes. No dramatic difference in fibrosis was found in mouse cardiac slices. Lenvatinib upregulates apoptosis-related protein expression. In addition, lenvatinib increased ERS-related protein expression (GRP78, CHOP, and ATF6) and enhanced PERK phosphorylation. In neonatal rat cardiac myocytes, lenvatinib markedly decreased the viability of cardiomyocytes and induced apoptosis. Furthermore, ROS production increased and MMP decreased. Similar to the mice experiment, lenvatinib caused upregulation of apoptosis-related and ERS-related proteins and increased the phosphorylation levels of PERK and IRE1α.
Conclusion: Lenvatinib-induced cardiotoxicity is associated with ERS-induced apoptosis by targeting the ATF6, IRE1α, and PERK signaling pathways.
{"title":"Tyrosine Kinase Inhibitor Lenvatinib Causes Cardiotoxicity by Inducing Endoplasmic Reticulum Stress and Apoptosis through Activating ATF6, IRE1α and PERK Signaling Pathways.","authors":"Siqi Wang, Fang Ji, Xiaoli Gao, Zhiyi Li, Si Lv, Juan Zhang, Jiarui Luo, Dan Li, Jie Yan, Huayang Zhang, Kaicheng Fang, Lin Wu, Miaoling Li","doi":"10.2174/0115748928265981231204044653","DOIUrl":"https://doi.org/10.2174/0115748928265981231204044653","url":null,"abstract":"<p><strong>Background: </strong>Lenvatinib is a tyrosine kinase inhibitor that can improve progression-free survival in patients with thyroid cancer and hepatocellular carcinoma. However, it is limited by adverse cardiovascular events, including hypertension and cardiac dysfunction. Activation of endoplasmic reticulum stress is involved in cardiomyocyte apoptosis.</p><p><strong>Objective: </strong>This study aimed to confirm whether the cardiotoxicity of lenvatinib is associated with endoplasmic reticulum stress by targeting the activating transcription factor 6 (ATF6), inositol- requiring enzyme 1α (IRE1α) and protein kinase RNA-like ER kinase (PERK) signaling pathways.</p><p><strong>Methods: </strong>Male C57/BL6 mice were intragastric administration with 30 mg/kg/day lenvatinib. Electrocardiography (ECG) and echocardiography were used to detect arrhythmias and cardiac function. Neonatal rat cardiomyocytes were treated with lenvatinib for 48h. Cell counting kit (CCK8), 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFHDA), Hoechst 33258 and dihydrorhodamine 123 were respectively used for evaluating cell viability, the level of reactive oxygen species (ROS), nuclear morphological changes and mitochondrial membrane potential (MMP) level.</p><p><strong>Results: </strong>Lenvatinib remarkably decreased the posterior wall thickness of left ventricle during diastole and systole but caused little decrease to the left ventricular ejection fraction (LVEF, %). Furthermore, lenvatinib greatly prolonged the corrected QT interval (QTc) and altered the morphology of cardiomyocytes. No dramatic difference in fibrosis was found in mouse cardiac slices. Lenvatinib upregulates apoptosis-related protein expression. In addition, lenvatinib increased ERS-related protein expression (GRP78, CHOP, and ATF6) and enhanced PERK phosphorylation. In neonatal rat cardiac myocytes, lenvatinib markedly decreased the viability of cardiomyocytes and induced apoptosis. Furthermore, ROS production increased and MMP decreased. Similar to the mice experiment, lenvatinib caused upregulation of apoptosis-related and ERS-related proteins and increased the phosphorylation levels of PERK and IRE1α.</p><p><strong>Conclusion: </strong>Lenvatinib-induced cardiotoxicity is associated with ERS-induced apoptosis by targeting the ATF6, IRE1α, and PERK signaling pathways.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The emergence of drug resistance to oxaliplatin (OXA) is one of the critical obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate the effect of Y6 on oxaliplatin resistance in HCC.
Methods: MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant cells and observed the morphological changes of the cells. At the same time, transwell assay was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and Western blot analysis were performed to determine the expression levels of the miR-338-3p gene, HIF-1α/Twist proteins, and EMT-related proteins.
Results: We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the control group and OXA group showed typical mesenchymal-like cell morphology, while most of the cells in co-administration groups showed typical epithelioid cell morphology, and the ability of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated.
Conclusion: Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT. Therefore, Y6 could be considered an effective medication resistance reversal agent, which could improve the therapeutic effect for hepatocellular cancer patients.
{"title":"Epigallocatechin Gallate Derivative Y6 Reverses Oxaliplatin Resistance in Hepatocellular Carcinoma via Targeting the MiR-338-3p/HIF-1α/TWIST Axis to Inhibit EMT.","authors":"Chuan Huang, Si-Hong Wang, Tao-Tao Liu, Mei-Yi Wu, Kai-Ning Cai, Zhan-Hong Xie, Rui-Qiang Zhao, Yan Wen","doi":"10.2174/0115748928293750240619092747","DOIUrl":"https://doi.org/10.2174/0115748928293750240619092747","url":null,"abstract":"<p><strong>Background: </strong>The emergence of drug resistance to oxaliplatin (OXA) is one of the critical obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate the effect of Y6 on oxaliplatin resistance in HCC.</p><p><strong>Methods: </strong>MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant cells and observed the morphological changes of the cells. At the same time, transwell assay was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and Western blot analysis were performed to determine the expression levels of the miR-338-3p gene, HIF-1α/Twist proteins, and EMT-related proteins.</p><p><strong>Results: </strong>We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the control group and OXA group showed typical mesenchymal-like cell morphology, while most of the cells in co-administration groups showed typical epithelioid cell morphology, and the ability of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated.</p><p><strong>Conclusion: </strong>Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT. Therefore, Y6 could be considered an effective medication resistance reversal agent, which could improve the therapeutic effect for hepatocellular cancer patients.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Natural compounds such as Berberine (Ber) have been considered due to favorable anticancer properties, low side effects, and availability along with chemotherapy treatments.
Objectives: This study aimed to investigate the radiosensitizing and radioprotective properties of Ber.
Methods: In this systematic review that was performed according to PRISMA 2020 guidelines, we searched the publications before 25 Sep 2023 in Web of Science, PubMed, Scopus, Embase, and Cochrane Library databases. After determining inclusion and exclusion criteria, data were extracted and imported into an Excel form, and the results of the studies were reviewed.
Results: Ber by reducing the levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and increasing interleukin 10 (IL-10) levels, showed its antioxidant and anti-inflammatory properties against ionizing radiation. Reducing cell cytotoxicity and apoptosis were other radioprotective properties of Ber. Conversely, in cancer cells, Ber, via inducing oxidative stress and accumulation ROS in tumor tissues, inducing DNA damage, mitochondrial dysfunction and hyperpolarization, inducing apoptosis, and cell cycle arrest, inhibits the up-regulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) revealed radiosensitizing properties.
Conclusion: Ber, via various mechanisms, showed favorable radioprotective and radiosensitizing properties in clinical and experimental studies. However, more clinical studies are needed in this field.
背景:小檗碱(Berberine,Ber)等天然化合物因其良好的抗癌特性、低副作用以及可与化疗药物同时使用而被认为是抗癌药物:本研究旨在探讨小檗碱的放射增敏和放射保护特性:本系统性综述根据 PRISMA 2020 指南进行,我们在 Web of Science、PubMed、Scopus、Embase 和 Cochrane Library 数据库中检索了 2023 年 9 月 25 日之前的出版物。确定纳入和排除标准后,提取数据并导入Excel表格,对研究结果进行回顾:Ber 通过降低活性氧(ROS)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)的水平,以及提高白细胞介素 10(IL-10)的水平,显示了其抗氧化和抗炎特性。减少细胞毒性和细胞凋亡是 Ber 的其他辐射保护特性。相反,在癌细胞中,Ber 通过诱导氧化应激和肿瘤组织中 ROS 的积累,诱导 DNA 损伤、线粒体功能障碍和超极化,诱导细胞凋亡和细胞周期停滞,抑制缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)的上调,显示出其放射致敏特性:结论:在临床和实验研究中,Ber 通过各种机制显示出良好的放射保护和放射致敏特性。然而,这一领域还需要更多的临床研究。
{"title":"Radiotherapy Enhancing and Radioprotective Properties of Berberine: A Systematic Review.","authors":"Elham Raeisi, Saeid Heidari-Soureshjani, Catherine Mt Sherwin, Zeinab Bagheri","doi":"10.2174/0115748928315442240624120104","DOIUrl":"https://doi.org/10.2174/0115748928315442240624120104","url":null,"abstract":"<p><strong>Background: </strong>Natural compounds such as Berberine (Ber) have been considered due to favorable anticancer properties, low side effects, and availability along with chemotherapy treatments.</p><p><strong>Objectives: </strong>This study aimed to investigate the radiosensitizing and radioprotective properties of Ber.</p><p><strong>Methods: </strong>In this systematic review that was performed according to PRISMA 2020 guidelines, we searched the publications before 25 Sep 2023 in Web of Science, PubMed, Scopus, Embase, and Cochrane Library databases. After determining inclusion and exclusion criteria, data were extracted and imported into an Excel form, and the results of the studies were reviewed.</p><p><strong>Results: </strong>Ber by reducing the levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and increasing interleukin 10 (IL-10) levels, showed its antioxidant and anti-inflammatory properties against ionizing radiation. Reducing cell cytotoxicity and apoptosis were other radioprotective properties of Ber. Conversely, in cancer cells, Ber, via inducing oxidative stress and accumulation ROS in tumor tissues, inducing DNA damage, mitochondrial dysfunction and hyperpolarization, inducing apoptosis, and cell cycle arrest, inhibits the up-regulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) revealed radiosensitizing properties.</p><p><strong>Conclusion: </strong>Ber, via various mechanisms, showed favorable radioprotective and radiosensitizing properties in clinical and experimental studies. However, more clinical studies are needed in this field.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}