南方医科大学学报2025,Vol.45Issue(7):1423-1433,11.DOI:10.12122/j.issn.1673-4254.2025.07.08
桂枝茯苓丸活性成分常春藤皂苷元通过抑制JAK2/STAT3通路抑制宫颈癌细胞的生长
Therapeutic mechanism of hederagenin,an active component in Guizhi Fuling Pellets,against cervical cancer in nude mice
摘要
Abstract
Objective To explore the therapeutic mechanism of Guizhi Fuling(GZFL)Pellets against cervical cancer.Methods Publicly available databases were used to identify the targets of GZFL Pellets and cervical cancer to construct the protein-protein interaction(PPI)network,followed by GO biological process and KEGG pathway enrichment analysis of the hub genes.The"Traditional Chinese Medicine-Active Ingredients-Targets-Pathways"network for GZFL Pellets in cervical cancer treatment was generated using Cytoscape v10.0.0,and molecular docking of the drug and potential targets was performed to predict the specific targets of active components in Guizhi Fuling Pellets.The inhibitory effects of hederagenin,an active ingredient in GZFL Pellets,was tested in cultured cervical cancer cells and in nude mice bearing cervical cancer xenografts.Results GZFL Pellets contain 338 active components targeting 247 action sites.A total of 10127 cervical cancer-related targets were obtained,and among them 195 were identified as potential therapeutic targets of GZFL Pellets for cervical cancer treatment,including the key targets of GABRA1,PTK2,JAK2,HTR3A,GSR,and IL-17.Molecular docking study showed low binding energies of the active components such as hederagenin,campesterol,and stigmasterol for protein-molecule interaction.GO enrichment analysis suggested that GZFL Pellets inhibited cervical cancer primarily by regulating responses to steroid hormones,oxidative stress,and lipopolysaccharides.Among the active components of GZFL Pellets,hederagenin was found to inhibit cervical cancer cells in vitro and significantly reduced STAT3 phosphorylation level in the cancer cells.In nude mice bearing cervical cancer xenografts,hederagenin effectively inhibited tumor growth rate without causing obvious adverse effects.Conclusion GZFL Pellets inhibit cervical cancer cell growth through its multiple active components that target different pathways.Among these components,hederagenin inhibits tumor cell growth possibly by directly binding to JAK2 protein to inhibit STAT3 phosphorylation.关键词
网络药理学/桂枝茯苓丸/宫颈癌/人乳头瘤病毒感染/常春藤皂苷元Key words
network pharmacology/Guizhi Fuling Pellets/cervical cancer/HPV infection/hederagenin引用本文复制引用
朱胤福,李怡燃,王奕,黄颖而,龚昆翔,郝文波,孙玲玲..桂枝茯苓丸活性成分常春藤皂苷元通过抑制JAK2/STAT3通路抑制宫颈癌细胞的生长[J].南方医科大学学报,2025,45(7):1423-1433,11.基金项目
国家自然科学基金(82304781,82404926) (82304781,82404926)
广东省基础与应用基础研究基金自然科学基金(2024A1515012978,2025A1515011316)Supported by National Natural Science Foundation of China(82304781,82404926). (2024A1515012978,2025A1515011316)