Current cancer drug targets最新文献

Introduction: Oxaliplatin is a third-generation platinum-based chemotherapeutic agent widely used for colorectal cancer treatment. However, its therapeutic application is limited by low solubility, systemic toxicity, and poor bioavailability.

Methods: Solid lipid nanoparticles (SLNs) were prepared using a micro-emulsion technique and further optimized via Box-Behnken Design (BBD), considering key formulation variables including Glyceryl Monostearate, Soya Lecithin, and Tween 80. Nanoparticles were characterized by in vitro drug release, drug loading, encapsulation efficiency, zeta potential, particle size, and polydispersity index (PDI). Cytotoxic efficacy against the HT-29 colorectal cancer cell line was evaluated using the Sulforhodamine B (SRB) assay.

Results: The optimized SLN formulation exhibited a mean particle size of 115.41 nm, PDI of 0.202, and zeta potential of +23.1 mV, indicating stability and efficient cellular uptake. Drug loading and encapsulation efficiency were 10.2 ± 0.4% and 92 ± 3.2%, respectively. In vitro release studies showed sustained drug release, reaching 97% over 48 hours. Cytotoxicity as-says demonstrated enhanced efficacy of Oxaliplatin SLNs, with IC₅₀ values of 0.9751 μg/mL at 24 h and 1.168 μg/mL at 48 h, compared to free Oxaliplatin (52.95 μg/mL at 24 h and 16.33 μg/mL at 48 h).

Discussion: GMS-based SLNs optimized with Tween 80, lecithin, and DDAB exhibited ideal size, charge, and high encapsulation. FTIR and DSC analyses confirmed component compatibility. The formulation showed sustained release and enhanced cytotoxicity, highlighting its potential to improve Oxaliplatin delivery and therapeutic efficacy in colorectal cancer.

Conclusion: The optimized Oxaliplatin SLNs demonstrated improved solubility, controlled release, and enhanced cytotoxicity, confirming their promise as a nanocarrier system for colorectal cancer therapy. Further in vivo studies are required to validate clinical effectiveness.

Introduction: This study aims to characterize the polypeptide expression profiles in omental metastasis of Ovarian Cancer (OC) and explore their potential applications in the treatment of OC metastasis.

Methods: Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) was employed to analyze the polypeptide profiles of primary OC tissues, omental metastatic tissues, and normal omental tissues from three OC patients. Differentially expressed polypeptides were screened using bioinformatics, and three polypeptides were synthesized to investigate their functional mechanisms in OC.

Results: LC-MS/MS analysis revealed 127 differentially expressed polypeptides in omental metastatic tissues compared to primary OC tissues, and 171 differentially expressed polypeptides compared to normal omental tissues. Notably, a polypeptide derived from alpha-2-macroglobulin (pAHSG) was significantly downregulated in omental metastatic tissues compared to both normal omental tissues and primary OC tissues. In vitro experiments demonstrated that pAHSG inhibited the proliferation and invasion of OC cells in a concentration-dependent manner. Flow cytometry further indicated an increase in G1 phase cells and a reduction in S phase cells following pAHSG treatment. Pull-down assays combined with mass spectrometry identified 40 proteins interacting with pAHSG, and KEGG pathway analysis revealed their involvement in aminoacyl-tRNA biosynthesis and cancer-related pathways. Collectively, these findings suggest that the downregulation of pAHSG is closely associated with omental metastasis in OC.

Discussion: The polypeptide expression profiles of omental metastatic tissues in OC exhibit significant alterations. The pAHSG effectively suppresses the malignant behaviors of OC cells, providing a novel potential target for the prevention and treatment of OC metastasis.

Conclusion: Compared with primary OC tissues and normal omental tissues, the polypeptide expression profiles of omental metastatic tissues exhibit significant alterations. Notably, pA-HSG, whose level is significantly changed in metastatic tissues, can effectively inhibit the malignant behaviors of OC cells, thereby providing a novel potential target for the treatment of OC metastasis.

The four-and-a-half LIM (FHL) protein family, a subgroup of the LIM-only super-family, consists of cysteine-rich cytoskeletal proteins characterized by four-and-a-half LIM domains. These proteins display tissue-specific expression and diverse cellular functions, and accumulating evidence has linked their dysregulation to tumorigenesis. FHL proteins influ-ence key biological processes, including transcriptional regulation, cytoskeletal remodeling, cell proliferation, and signaling pathway modulation, thereby contributing to cancer initiation and progression. Depending on cellular and tissue context, they may function either as tumor suppressors or as oncogenic drivers. Recent studies have highlighted their diagnostic and prog-nostic potential, as aberrant expression of FHL proteins correlates with clinical outcomes in multiple malignancies. Moreover, growing attention has been directed toward their therapeutic relevance, with efforts focusing on targeting upstream regulatory mechanisms to modulate FHL activity. This review provides an integrated overview of the structural and functional features of the FHL protein family, summarizes current understanding of their roles in cancer biology, and discusses their potential as biomarkers and therapeutic targets. By outlining the mechanisms underlying their dysregulation, this work offers new perspectives on the biologi-cal significance of FHL proteins and their implications for cancer research and clinical prac-tice.

Introduction: Melanoma is a highly aggressive skin cancer that arises from transformed epidermal melanocytes and is one of the malignancies with the fastest proliferation rates globally. Angiogenesis has been identified as a critical target for melanoma therapy, and endostatin has been verified to impede endogenous angiogenesis. However, some patients' therapeutic responses remain unsatisfactory. CD24, which functions as an anti-phagocytic signal, represents a potential target for tumor immunotherapy. Thus, in this study, we investigated the anti-melanoma effects of combined CD24 inhibition and endostatin treatment.

Materials and methods: The co-expressed plasmid was constructed for functional verification. A melanoma-bearing mouse model was used to observe changes in tumor size during treatment. Protein expression, apoptosis, immune cell infiltration, and macrophage subset proportions were measured using Western blot, immunofluorescence, TUNEL, and flow cytometry assays.

Results: The co-expressed plasmid significantly inhibited CD24 and VEGF expression in cells. The combination therapy promoted tumor cell apoptosis and decreased angiogenesis. It also increased infiltration of M1 macrophages, T lymphocytes, and NK cells in tumor tissue and the spleen. The combined plasmid-based therapy considerably suppressed tumor growth and lengthened the survival time of mice.

Discussion: The combination therapy remodeled the immunosuppressive tumor microenvironment, enhancing M1 macrophage and T lymphocyte infiltration while suppressing angiogenesis via dual inhibition of CD24 and VEGF.

Conclusion: Combining CD24 inhibition with antiangiogenic therapy could offer a novel therapeutic strategy for melanoma.

Background: Lung cancer remains the leading cause of cancer mortality worldwide, underscoring the need for non-invasive early diagnostic tools. IP-10, a cytokine involved in inflammation and angiogenesis, is a promising candidate. The present study aims to assess the relevance of IP-10 in lung cancer early diagnosis.

Methods: In this cross-sectional study, we measured serum IP-10 levels using Luminex assays in 52 treatment-naïve lung cancer patients without comorbidities and 14 healthy controls. Based on the non-normal distribution of data, group comparisons were performed using Wilcoxon rank-sum tests. Multivariate linear regression was used to adjust for cofounders.

Results: IP-10 levels were significantly elevated in lung cancer patients compared to healthy controls (median: 189.69 pg/mL vs. 108.78 pg/mL, p = 0.001). This significance persisted in the early-stage subgroup (stages 0-IIA; median: 192.49 pg/mL vs. 108.78 pg/mL, p = 0.001), even after multivariate adjustment (p = 0.018). Levels peaked in evolved early-stage disease (median: 241.42 pg/mL) before declining in advanced stages, while remaining elevated above controls.

Discussion: The rise in IP-10 levels in early-stage lung cancer patients emphasizes its potential to serve as an early diagnostic biomarker. Meanwhile, the peak-and-decline pattern during phases of disease is consistent with its postulated dual role in early antitumor immunity and later tumor promotion.

Conclusion: IP-10 can potentially be used as a supplemental serum biomarker for early lung cancer diagnosis. This finding calls for additional validation in bigger, multi-center cohorts to define diagnostic thresholds and investigate their incorporation into multi-marker panels.

Introduction: Multidrug resistance (MDR) remains a major obstacle in the treatment of epithelial ovarian cancer (EOC). This study aimed to elucidate the regulatory role of FBXW7 in modulating the HSF-1/P-glycoprotein (P-gp) signalling axis and its impact on MDR in ovarian cancer.

Materials and methods: Quantitative PCR, western blotting, immunohistochemistry, and immunofluorescence were employed to assess FBXW7, HSF-1, and P-gp expression in ovarian tissues and cell lines. Functional assays, including CCK-8 proliferation assays and lentiviral-mediated gene modulation, were conducted in SKOV3 and cisplatin-resistant SKOV3/DDP cells to evaluate the effects of FBXW7 on cell proliferation and drug resistance-associated pathways.

Results: FBXW7 expression was markedly reduced in ovarian cancer tissues compared to normal controls and positively correlated with patient progression-free survival. Overexpression of FBXW7 suppressed proliferation in both SKOV3 and SKOV3/DDP cells and led to decreased HSF-1 and P-gp expression. Conversely, FBXW7 knockdown enhanced cell proliferation and upregulated the HSF-1/P-gp axis. Immunohistochemical and immunofluorescence analyses confirmed an inverse expression pattern between FBXW7 and HSF-1 in patient tissues.

Discussion: The findings revealed FBXW7 to suppress multidrug resistance in ovarian cancer by downregulating the HSF-1/P-gp axis, thereby enhancing chemosensitivity. This study has highlighted a novel regulatory mechanism and suggested that restoring FBXW7 function may offer therapeutic benefit in overcoming chemoresistance.

Conclusion: FBXW7 acts as a tumour suppressor that mitigates MDR in ovarian cancer by negatively regulating the HSF-1/P-gp pathway. The findings have offered mechanistic insights into chemoresistance and highlight the therapeutic potential of targeting FBXW7-HSF-1 signaling in EOC management.

Purpose: Currently, there is limited information available regarding the clinical features, pathological findings, and detailed molecular characteristics of pleomorphic xan-thoastrocytoma (PXA) and epithelioid glioblastoma (eGBM).

Methods: In this study, we examined 11 PXA cases [9 grade 2 PXA (PXA G2) and 2 grade 3 PXA (PXA G3)] as well as 15 eGBM cases to investigate their histopathological and molecular associations.

Results: Morphologically, PXA and eGBM exhibited distinct histological features. However, immunohistochemical analysis revealed no consistent differences between these glioma sub-types, with the exception of the Ki-67 labeling index. BRAF V600E mutation was detected in 60.0% of PXA cases and 85.7% of eGBM cases through immunohistochemistry (IHC) and/or sequencing, with complete concordance between the two methods. Molecular analysis further revealed that TERT promoter (TERT-p) mutation and copy number abnormalities were more prevalent in eGBM than in PXA.

Conclusion: In conclusion, PXA and eGBM share similar clinical characteristics but exhibit different histological features. From a molecular perspective, PXA and eGBM belong to the same category and progress through the accumulation of genetic abnormalities, including TERT-p mutations, CDKN2A/B deletions, and TP53 mutations, based on the presence of BRAF mutation; however, larger sample sizes are required for validation.

Introduction: As a common herbal medicine, Cuscuta chinensis Lam is widely used for cancer treatment in China. However, the anti-lung cancer effect of the bioactive constituents in C. chinensis and, the potential molecular mechanisms of action have yet to be elucidated.

Materials and methods: Bioassay-guided fractionation was used to isolate luteolin from the water extract of C. chinensis (CLW). The structure of luteolin was determined by spectroscopic analysis. The viability of A549 and H1650 lung cancer cells was determined using the MTT assay. Annexin V-FITC staining assay and cell cycle analysis were performed to explore the apoptosis and cell cycle phase distribution of lung cancer cells, respectively. Transwell invasion, wound healing, transwell migration, and adhesion assays were conducted to observe the lung cancer cell invasion, migration, and adhesion. Protein expression was determined via Western blot analysis.

Results and discussion: Luteolin was isolated from CLW by bioassay-guided fractionation, and its structure was determined by HR-ESI-MS and NMR. Luteolin inhibited the viability of A549 and H1650 lung cancer cells in a dose and time-dependent manner. Luteolin also dose-dependently induced apoptosis, and arrested the cell cycle at the G0/G1 phase in both cell types. Treatment with luteolin dose-dependently inhibited the invasion, migration, and adhesion of these cells. Luteolin consistently up-regulated FOSB, FGFBP1, and NPTX1 protein expression levels, and down-regulated H3K9me3, SETDB1, and MAP2K6 protein expression levels in A549 and H1650 cells. Co-treatment of luteolin and mithramycin A on A549 and H1650 lung cancer cells exhibited stronger up-regulation of FOSB and NPTX1 protein expression levels, and stronger down-regulation of SETDB1, H3K9me3, and MAP2K6 protein expression levels than luteolin or mithramycin A treatment alone. Co-treatment of luteolin and mithramycin A synergistically inhibited A549 and H1650 cell viability; induced apoptosis; delayed cell cycle at the G0/G1 phase; and inhibited the invasion, migration, and adhesion of A549 and H1650 cells compared with the treatment of luteolin or mithramycin A alone.

Conclusion: Luteolin may suppresses the viability, invasion, migration, and adhesion of lung cancer cells via co-treatment with mithramycin A.

Introduction: Tongue Squamous Cell Carcinoma (TSCC) is a prevalent head and neck malignancy with limited targeted therapies and minimal toxicity. Sodium Cantharidate (SCA), a natural compound, exhibits anti-tumor potential, but its molecular targets in TSCC remain undefined. This study aimed to evaluate SCA's anti-TSCC efficacy in preclinical models and elucidate its mechanism of action.

Methods: SCA's effects on TSCC cells were assessed using CCK-8 viability, scratch wound healing, Transwell migration/invasion, and flow cytometry (apoptosis). Efficacy was further evaluated in nude mouse xenograft models and patient-derived TSCC organoids. Molecular mechanisms were investigated via Western blotting.

Results: SCA significantly inhibited TSCC cell proliferation, migration, and invasion, and induced dose-dependent apoptosis in vitro. It demonstrated cytotoxicity in xenografts and organoids. Western blotting showed SCA upregulated p53 protein and phosphorylation at Ser33, Ser37, and Ser46. Pro-apoptotic BAX and cleaved Caspase 3 increased, while anti-apoptotic BCL-2 decreased, significantly lowering the BCL-2/BAX ratio.

Discussion: SCA attenuates TSCC growth and invasion in vitro and in vivo, primarily by inducing apoptosis through modulation of p53 phosphorylation. This is the first study to validate SCA's efficacy using patient-derived TSCC organoids, highlighting their value for pre-clinical drug assessment. While promising, further mechanistic depth is warranted. The results support SCA's potential for clinical translation.

Conclusion: SCA potently inhibits TSCC progression in cell lines, xenografts, and patient-derived organoids. Its mechanism involves activation of p53 phosphorylation, shifting the BCL-2/BAX balance, and triggering caspase-dependent apoptosis. These findings position SCA as a promising therapeutic candidate and underscore the utility of organoid models in oncology drug development.

Ovarian cancer remains the most lethal gynecologic malignancy, characterized by a poor prognosis that is mainly attributable to frequent disease recurrence and the development of chemoresistance. Central to its aggressive phenotype is the population of ovarian cancer stem cells (OCSCs), which exhibit self-renewal capacity, tumor-initiating potential, and remarkable adaptive abilities. The tumor microenvironment (TME) critically sustains these properties by providing a protective niche that maintains the stemness of OCSCs and promotes malignant behaviors. The TME comprises diverse cellular and molecular components, including immune cells, cancer-associated fibroblasts, the extracellular matrix, and soluble factors. These elements interact with OCSCs through intricate signaling networks, enhancing stem-like properties, facilitating immune evasion, and conferring resistance to conventional chemotherapy. Consequently, targeting the TME has emerged as a promising therapeutic strategy to disrupt these supportive interactions and effectively eliminate OCSCs. In this review, we systematically summarize the mechanisms by which key TME components regulate the maintenance of OCSCs' stemness, metastasis, and chemoresistance. Additionally, we highlight recent advances in therapeutic strategies targeting the microenvironment of OCSCs and discuss their efficacy, potential clinical applications, and associated translational challenges. This work aims to establish a comprehensive theoretical framework for developing novel targeted therapies that can effectively eradicate OCSCs, reverse chemoresistance, and ultimately improve clinical outcomes in patients with ovarian cancer.