Yu Qi, Bo Xu, Jinrong He, Bo Jiang, Le Yan, Haiyan Zhou, Saili Chen
{"title":"逍遥散结汤治疗三阴性乳腺癌的机制及疗效：网络药理学及实验验证方法。","authors":"Yu Qi, Bo Xu, Jinrong He, Bo Jiang, Le Yan, Haiyan Zhou, Saili Chen","doi":"10.2147/DDDT.S492047","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Triple-negative breast cancer (TNBC) is a disease associated with high incidence and high mortality, which is a major problem threatening women's health. Xiaoyao Sanjie Decoction (XYSJD) exhibits remarkable therapeutic efficacy on TNBC; however, the underlying mechanism is unclear. This study verified the efficacy of XYSJD and its active component in the treatment of TNBC and explored its potential mechanism.</p><p><strong>Methods: </strong>Ultra-high performance liquid chromatography-hybrid quadrupole orbitrap mass spectrometry (UHPLC-Q Exactive HFX-MS) was applied to explore the main chemical constituents of XYSJD. The key targets and potential mechanisms of XYSJD in the treatment of TNBC were predicted through network pharmacology, bioinformatics analysis and molecular docking. The effects of XYSJD against TNBC cells were evaluated by CCK-8 assay, EdU assay, wound healing assay, transwell assay, Hoechst-PI staining and flow cytometry. The mechanism of action was validated by Western blot analysis. Finally, the effect and mechanism of XYSJD and Que on TNBC were further verified by the tumor formation model.</p><p><strong>Results: </strong>UHPLC-Q Exactive HFX-MS identified a total of 9 compounds in XYSJD. Network pharmacological methods identified 206 targets for anti-TNBC. Bioinformatics analysis suggests that the EZH2/AKT1 signaling pathway might play an important role in the effects of XYSJD against TNBC. Gene Ontology enrichment analysis showed that the biological process of XYSJD in TNBC treatment mainly involved apoptosis. XYSJD and Que were observed to have a good anticancer effect in vivo and in vitro. In addition, quercetin could induce the apoptosis of TNBC cells by decreased the expression levels of EZH2/AKT1 signaling pathway. Furthermore, AKT1 overexpression, treatment with the AKT activator (SC79) and EZH2 overexpression could reverse apoptosis induced by quercetin in TNBC cells.</p><p><strong>Conclusion: </strong>This study revealed the anti-TNBC efficacy of XYSJD. Quercetin, the effective component of XYSJD, promoted apoptosis of TNBC cells via blockade of the EZH2/AKT1 signaling pathway. These findings aim to provide a more reliable basis for the clinical application of XYSJD in the treatment of TNBC.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"6263-6281"},"PeriodicalIF":4.7000,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687282/pdf/","citationCount":"0","resultStr":"{\"title\":\"Unveiling the Mechanisms and Therapeutic Effects of Xiaoyao Sanjie Decoction in Triple-Negative Breast Cancer: A Network Pharmacology and Experimental Validation Approach.\",\"authors\":\"Yu Qi, Bo Xu, Jinrong He, Bo Jiang, Le Yan, Haiyan Zhou, Saili Chen\",\"doi\":\"10.2147/DDDT.S492047\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Triple-negative breast cancer (TNBC) is a disease associated with high incidence and high mortality, which is a major problem threatening women's health. Xiaoyao Sanjie Decoction (XYSJD) exhibits remarkable therapeutic efficacy on TNBC; however, the underlying mechanism is unclear. This study verified the efficacy of XYSJD and its active component in the treatment of TNBC and explored its potential mechanism.</p><p><strong>Methods: </strong>Ultra-high performance liquid chromatography-hybrid quadrupole orbitrap mass spectrometry (UHPLC-Q Exactive HFX-MS) was applied to explore the main chemical constituents of XYSJD. The key targets and potential mechanisms of XYSJD in the treatment of TNBC were predicted through network pharmacology, bioinformatics analysis and molecular docking. The effects of XYSJD against TNBC cells were evaluated by CCK-8 assay, EdU assay, wound healing assay, transwell assay, Hoechst-PI staining and flow cytometry. The mechanism of action was validated by Western blot analysis. Finally, the effect and mechanism of XYSJD and Que on TNBC were further verified by the tumor formation model.</p><p><strong>Results: </strong>UHPLC-Q Exactive HFX-MS identified a total of 9 compounds in XYSJD. Network pharmacological methods identified 206 targets for anti-TNBC. Bioinformatics analysis suggests that the EZH2/AKT1 signaling pathway might play an important role in the effects of XYSJD against TNBC. Gene Ontology enrichment analysis showed that the biological process of XYSJD in TNBC treatment mainly involved apoptosis. XYSJD and Que were observed to have a good anticancer effect in vivo and in vitro. In addition, quercetin could induce the apoptosis of TNBC cells by decreased the expression levels of EZH2/AKT1 signaling pathway. Furthermore, AKT1 overexpression, treatment with the AKT activator (SC79) and EZH2 overexpression could reverse apoptosis induced by quercetin in TNBC cells.</p><p><strong>Conclusion: </strong>This study revealed the anti-TNBC efficacy of XYSJD. Quercetin, the effective component of XYSJD, promoted apoptosis of TNBC cells via blockade of the EZH2/AKT1 signaling pathway. These findings aim to provide a more reliable basis for the clinical application of XYSJD in the treatment of TNBC.</p>\",\"PeriodicalId\":11290,\"journal\":{\"name\":\"Drug Design, Development and Therapy\",\"volume\":\"18 \",\"pages\":\"6263-6281\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-12-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687282/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Design, Development and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DDDT.S492047\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S492047","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Unveiling the Mechanisms and Therapeutic Effects of Xiaoyao Sanjie Decoction in Triple-Negative Breast Cancer: A Network Pharmacology and Experimental Validation Approach.
Purpose: Triple-negative breast cancer (TNBC) is a disease associated with high incidence and high mortality, which is a major problem threatening women's health. Xiaoyao Sanjie Decoction (XYSJD) exhibits remarkable therapeutic efficacy on TNBC; however, the underlying mechanism is unclear. This study verified the efficacy of XYSJD and its active component in the treatment of TNBC and explored its potential mechanism.
Methods: Ultra-high performance liquid chromatography-hybrid quadrupole orbitrap mass spectrometry (UHPLC-Q Exactive HFX-MS) was applied to explore the main chemical constituents of XYSJD. The key targets and potential mechanisms of XYSJD in the treatment of TNBC were predicted through network pharmacology, bioinformatics analysis and molecular docking. The effects of XYSJD against TNBC cells were evaluated by CCK-8 assay, EdU assay, wound healing assay, transwell assay, Hoechst-PI staining and flow cytometry. The mechanism of action was validated by Western blot analysis. Finally, the effect and mechanism of XYSJD and Que on TNBC were further verified by the tumor formation model.
Results: UHPLC-Q Exactive HFX-MS identified a total of 9 compounds in XYSJD. Network pharmacological methods identified 206 targets for anti-TNBC. Bioinformatics analysis suggests that the EZH2/AKT1 signaling pathway might play an important role in the effects of XYSJD against TNBC. Gene Ontology enrichment analysis showed that the biological process of XYSJD in TNBC treatment mainly involved apoptosis. XYSJD and Que were observed to have a good anticancer effect in vivo and in vitro. In addition, quercetin could induce the apoptosis of TNBC cells by decreased the expression levels of EZH2/AKT1 signaling pathway. Furthermore, AKT1 overexpression, treatment with the AKT activator (SC79) and EZH2 overexpression could reverse apoptosis induced by quercetin in TNBC cells.
Conclusion: This study revealed the anti-TNBC efficacy of XYSJD. Quercetin, the effective component of XYSJD, promoted apoptosis of TNBC cells via blockade of the EZH2/AKT1 signaling pathway. These findings aim to provide a more reliable basis for the clinical application of XYSJD in the treatment of TNBC.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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