基于网络药理学预测“人参-五味子”药对治疗肺癌的作用机制

Prediction of Mechanism of"Renshen-Wuweizi(Panax ginseng-Schisandra chinensis)"in Treatment of Lung Cancer Based on Network Pharmacology

目的基于网络药理学方法预测“人参-五味子”配伍对防治肺癌的可能作用机制。方法依托TCMP数据库及平台,检索人参-五味子中药化学成分、作用靶点,并通过TCGA数据库获取肺癌差异基因,预测药对中肺癌相关的作用靶点,构建“化合物-靶点”网络模型。通过STRING平台构建蛋白互作网络(PPI),将筛选出的核心靶点提交到DAVID数据库进行基因富集分析,获得GO生物功能及KEGG信号通路注释结果,构建的“靶点-通路”网络。结果共筛选出29个候选活性成分,180个化合物靶点,39个肺癌相关潜在靶点;蛋白互作网络模型中,筛选出21个关键靶蛋白,基因富集分析显示,21个核心靶点涉及61个GO生物功能条目,包括:生物过程条目32个,细胞组成条目8个,分子功能条目21个;涉及KEGG信号通路共14条,涉及固醇类激素的合成、代谢途径、细胞色素P450代谢及钙信号通路。结论“人参-五味子”配伍通过调控机体激素及致癌物质代谢、免疫耐药、炎症反应,对肺癌发生、转移及耐药发挥防治作用。

Objective To predict the possible mechanism of"Renshen-Wuweizi(Panax ginseng-Schisandra chinensis)"compatibility in the prevention and treatment of lung cancer based on network pharmacology.Methods Based on the TCMP database and platform,the active components of"Renshen-Wuweizi(Panax ginseng-Schisandra chinensis)"were screened by pharmacokinetic parameters(ADME),and the lung cancer differential gene was obtained by TCGA database to predict the target of co-expressionand draw a"compound-target"network model.The protein interaction network(PPI)was constructed by STRING platform,and the core targets were screened and submitted to the DAVID database for gene enrichment analysis.The results of GO biological function and KEGG signaling pathway were obtained to construct a visual"compound-target-path"network and perform topology analysis on the network.Results A total of 5735 lung cancer differential genes were obtained.A total of 29 candidate active components,180 compound targets,and 39 lung cancer-related potential targets were screened out.In the protein interaction network model,21 key target proteins were screened.Gene enrichment analysis showed that 21 core targets were involved.There were 61 GO biological function items,including 32 biological process items,8 cell component entries,21 molecular function itemsand 14 KEGG signaling pathways,in which the target was significantly enriched in the synthesis and metabolism of steroid hormones pathways,cytochrome P450 metabolismand calcium signaling pathways.Conclusion"Renshen-Wuweizi(Panax ginseng-Schisandra chinensis)"may play an important role in the regulation and treatment of lung cancer,metastasis and drug resistance by regulating the metabolism,immune resistance and inflammatory reaction of body hormones and carcinogens.