基于网络药理学和分子对接探讨山药治疗胃癌的作用机制

Exploring mechanism of action of Rhizoma Dioscoreae in the treatment of gastric cancer based on network pharmacology and molecular docking

目的基于网络药理学和分子对接探讨山药治疗胃癌的潜在靶点及作用机制。方法通过网络公开数据库筛选出山药的有效成分和潜在靶点及胃癌的相关基因,并绘制二者的交集基因,在Cytoscape 3.8.0中完成山药有效成分-靶点-胃癌的可视化分析,运用药物与疾病的交集基因构建蛋白质-蛋白质互作网络图(protein-protein interaction,PPI),并采用拓扑分析得到核心靶点,使用Rx644.1.2进行基因本体(gene ontology,GO)生物学过程富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,利用AutoDock 1.5.7软件和PyMOL软件完成中药成分和疾病靶点间的分子对接。结果共筛选出山药的有效成分12个及潜在靶点119个,与胃癌的共同靶点56个。拓扑分析筛选出TP53、HSP90AA1、AKT1可能为山药治疗胃癌的关键靶点。GO富集分析一共得到1417个条目,KEGG富集分析共筛选出112条通路。分子对接结果显示AKT1与豆甾醇结合活性最强。结论初步揭示了山药通过多项成分、多个靶点及多条通路发挥对抗胃癌的作用,其药物成分和靶点可有效结合。

Objective To explore the mechanism of action of Rhizoma Dioscoreae in the treatment of gastric cancer based on network pharmacology and molecular docking.Methods The active compounds and potential targets of Rhizoma Dioscoreae,as well as gastric cancer associated gene targets,were retrieved from publicly available databases,and the intersection genes of the two were drawn.Visualization analysis of“active component of Rhizoma Dioscoreae-target-gastric cancer”was completed using Cytoscape 3.8.0 software.A protein-protein interaction network graph(PPI)was constructed for the intersection genes of drugs and diseases,and topological analysis was performed to obtain the core targets.Rx644.1.2.was used to analyze the enrichment of gene ortology function and kyoto encyclopedia of genes and genomes pathway.Autodoc 1.5.7 software and PyMOL software were used to complete the molecular docking between TCM components and disease targets.Results A total of 12 active components and 119 targets of Rhizoma Dioscoreae were screened out,as well as 56 common targets with gastric cancer.Topological analysis showed that TP53,HSP90AA1 and AKT1 might be the key targets of Rhizoma Dioscoreae in the treatment of gastric cancer.A total of 1417 items were obtained by GO functional enrichment analysis,and 112 pathways were screened by KEGG pathway enrichment analysis.Molecular docking results showed that AKT1 had the strongest binding activity to stigmasterol.Conclusion This study preliminarily revealed the anti-cancer effects of Rhizoma Dioscoreae on gastric cancer by multiple components,targets,and pathways,and its drug components and targets can effectively bird.