基于网络药理学和分子对接技术探讨益肠散结汤治疗结直肠癌的作用机制

Discussion on the Mechanism of Yichang Sanjie Decoction in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking Technology

基于网络药理学和分子对接技术探讨益肠散结汤对结直肠癌的作用机理。使用TCMSP、B atman-TCM和Swiss Target Prediction数据库获得益肠散结汤成分和作用靶点并进行筛选,以“colorectal cancer”、“colorectal carcinoma”和“colon cancer”为关键词在Therapeutic Target Database、Gene Cards和Drugbank数据库中得到疾病关联靶点,并获取交集靶点,可视化中药-成分-靶点-疾病网络,然后使用STRING数据库分析靶蛋白互作,再采用Cytoscape 3.7.1软件绘制互作图;利用R语言对GO功能和KEGG富集分析;使用Auto Dock和PyMOL软件可视化分子对接预测结果。筛选获取益肠散结汤有效成分76个,靶点188个,结直肠癌靶点11853个,交集靶点153个,GO功能富集分析生物过程2244个、细胞组成1 260条和分子功能203条,KEGG富集通路171条,分子对接结果显示槲皮素与TP53、EGFR、TNF和IL-6结合较好。益肠散结汤中槲皮素、木犀草素、柚皮素、β-谷甾醇和常春藤皂苷元等活性成分可能调节TP53、EGFR、TNF、ESR1、VEGFA、PTGS2和EGF等靶点,通过IL-17信号通路,肿瘤坏死因子信号通路,Th17细胞分化通路,HIF-1信号通路等通路参与细胞凋亡、细胞迁移和细胞侵袭,调控肿瘤血管生成。

To explore the mechanism of Yichang Sanjie Decoction on colorectal cancer based on network pharmacology and molecular docking technology.Firstly,TCMSP,Batman-TCM,Swiss Target Prediction database was used to obtain the components and targets of Yichang Sanjie Decoction,and Uniprot database was applied for converting gene names.Secondly,acquiring relevant disease targets in Therapeutic Target Database,Gene Cards and Drugbank databases with"colorectal cancer","colorectal carcinoma","colon cancer"as the key word,and obtaining the intersection targets with Venny2.1 to construct the network of"traditional Chinese medicine-ingredients-targets-diseases".Thirdly,using STRING database to analyze protein interaction,drawing PPI protein network diagram by Cytoscape software,and realizing GO and KEGG enrichment analysis through the R programming language.And then the molecular docking prediction and visualization results were displayed by AutoDock and PyMOL software.There were 76 active ingredients,188 targets,11853 disease targets,153 intersection targets,2244 GO enrichment biological processes,1260 cell components,203 molecular functions and 171 KEGG enrichment pathways in Yichang Sanjie Decoction.The results of molecular docking indicated that quercetin had good binding ability with TP53,EGFR,TNF,IL6.Quercetin,luteolin,naringenin,β-sitosterol,hederagenin and other active ingredients in YichangSanjie Decoction may regulate TP53,EGFR,TNF,ESR1,VEGFA,PTGS2,EGF and other targets,and control cell apoptosis,cell migration,cell growth and tumor angiogenesis through IL-17 signaling pathway,tumor necrosis factor signaling pathway,Th17 cell differentiation pathway and HIF-1 signaling pathway.