基于网络药理学和分子对接探讨小柴胡汤治疗乳腺癌的作用机制

Mechanism of Xiaochaihu Decoction(小柴胡汤) on Breast Cancer based on Network Pharmacology Methods and Molecular Docking

目的 基于网络药理学与分子对接方法探究小柴胡汤治疗乳腺癌的作用机制。方法 采用中药系统药理学数据库和分析平台(TCMSP)对小柴胡汤的化学成分和靶点进行筛选,并通过Uniprot数据库将靶点转化为相应的Gene Symbol,从GeneCards数据库检索乳腺癌疾病基因,运用Cytoscape 3.9.0构建小柴胡汤化学成分-靶点的网络图,再通过STRING 11.5数据库获得交集基因的蛋白互作(PPI)网络,运用插件CytoNCA筛选核心靶点,通过DAVID6.8数据库对交集基因进行了GO和KEGG富集分析,并对具有高拓扑分析度值的化学成分和靶标进行了分子对接。结果 获得小柴胡汤化学成分165个,乳腺癌疾病靶点筛选后保留950个,交集靶点118个,经GO和KEGG富集分析,发现其主要生物功能是药物反应、RNA聚合酶II启动子转录的正调控和DNA模板转录的正调控等。富集主要集中在癌症途径,分子对接显示山柰酚与AR结合最佳。结论 小柴胡汤治疗乳腺癌的主要化学成分为槲皮素、山柰酚、汉黄芩素,主要通过HSP90AA1、AR、ESR1等靶点发挥治疗作用。

Objective To explore the mechanism of Xiaochaihu Decoction(小柴胡汤) in the treatment of breast cancer based on network pharmacology and molecular docking.Methods The chemical composition and targets of Xiaochaihu decoction were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP),and the targets were converted into corresponding Gene Symbol via Uniprot database,and the breast cancer disease genes were searched from Gene Cards database.Using Cytoscape 3.9.0 We constructed a chemical-target network of Xiaochaihu decoction.Then,the protein-protein interaction( PPI) network of intersection genes is obtained through the STRING11.5 database,the core targets are screened by using the plug-in Cyto NCA,Crossover genes were enriched for GO and KEGG using the DAVID6.8 database,and molecular docking was performed for chemicals and targets with high topological assay values.Results We got 165Chemical ingredients of Xiaochaihu decoction.Breast cancer disease target screens retained 950 and crossover targets 118.After GO and KEGG enrichment analysis,we found that its main biological functions are drug response,positive regulation of RNA polymerase II promoter transcription,and positive regulation of DNA template transcription.The enrichment is mainly concentrated in the cancer pathway.Molecular docking shows that kaempferol binds best to AR.Conclusion The main active ingredients of Xiaochaihu decoction in the treatment of breast cancer are quercetin,kaempferol and wogonin,which mainly exert therapeutic effects through HSP90AA1,AR,ESR1 and other targets.