基于网络药理学和分子对接技术探讨泽漆汤治疗非小细胞肺癌的作用机制

Investigation on the function mechanism of Zeqi Decoction in the treatment of non-small cell lung cancer based on network pharmacology and molecular docking technology

目的采用网络药理学和分子对接技术,探讨泽漆汤治疗非小细胞肺癌(NSCLC)的作用机制。方法通过TCMSP、GeneCards、OMIM、TTD、DrugBank、PharmGKD以及String数据库获得泽漆汤活性成分、作用靶点以及NSCLC相关疾病靶点,采用Cytoscape 3.8.0软件绘制“活性成分-靶点-疾病”网络图,采用String数据库进行蛋白质-蛋白质相互作用(PPI)分析并绘制网络图,使用DAVID数据库进行基因本体(GO)和京都基因和基因组百科全书(KEGG)通路富集分析,使用AutoDock软件对关键活性成分和核心靶点进行分子对接。结果共筛选出178个泽漆汤活性成分和189个药物-疾病共有靶点,GO功能和KEGG通路富集分析显示泽漆汤可能通过RNA聚合酶Ⅱ启动子转录的正调控、细胞因子介导的信号通路、DNA模板转录的正调控、基因表达的正向调控、凋亡过程的负调控等生物学过程,调控肿瘤蛋白P53、AP-1转录因子、AKT/蛋白激酶B信号等关键靶点的表达,进一步调控癌症通路、脂质与动脉粥样硬化通路、AGE-RAGE信号通路、乙型肝炎、前列腺癌等信号通路,从而治疗NSCLC。分子对接结果显示,泽漆汤中活性成分与核心靶点间存在分子结合位点。结论泽漆汤能通过多成分、多靶点、多通路、多机制治疗NSCLC。

Objective To investigate the function mechanism of Zeqi Decoction in the treatment of non-small cell lung cancer(NSCLC)by using network pharmacology and molecular docking technology.Methods The active ingredients,function targets and NSCLC-related disease targets of Zeqi Decoction were obtained by TCMSP,GeneCards,OMIM,TTD,DrugBank,PharmGKD and String databases.The network diagram of"active ingredients-targets-diseases"was drawn by Cytoscape 3.8.0 software.protein-protein interaction(PPI)was analyzed with String database and the network diagram was drawn.The pathway enrichment analysis of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)was conducted using DAVID database.And molecular docking of key active ingredients and key targets was performed with AutoDock software.Results A total of 178 active ingredients of Zeqi Decoction and 189 drug-disease common targets were screened out.The enrichment analysis of GO function and KEGG pathway showed that Zeqi Decoction might be involved in biological processes such as positive regulation of RNA polymeraseⅡpromoter transcription,cytokine-mediated signal pathway,positive regulation of DNA template transcription,positive regulation of gene expression and negative regulation of apoptosis process,etc.,so as to regulate the expression of tumor protein P53,AP-1 transcription factor,AKT/protein kinase B signal and other key targets,and further regulate the signal pathways such as cancer,lipid and atherosclerosis,AGE-RAGE signal pathway,hepatitis B and prostate cancer,thereby treating NSCLC.The results of molecular docking showed that there were molecular binding sites between the active ingredients and the key targets in Zeqi Decoction.Conclusion Zeqi Decoction can treat NSCLC through multiple ingredients,multiple targets,mul tiple pathways,and multiple mechanisms.