网络药理学联合GEO数据挖掘与分子对接探究桔梗-鱼腥草治疗非小细胞肺癌的作用机制

Network Pharmacology Combined with GEO Data Mining and Molecular Docking to Explore the Mechanism of Action of Platycodonis Radix and Houttuyniae Herba in the Treatment of Non-Small Cell Lung Cancer

目的:通过网络药理学联合GEO数据挖掘以及分子对接技术探究桔梗-鱼腥草药对治疗非小细胞肺癌(NSCLC)的作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)数据库搜集桔梗-鱼腥草活性成分及其作用靶点,在Gencards、OMIM和GEO数据库获取疾病相关靶点,将二者靶点取交集获取桔梗-鱼腥草与NSCLC的共同靶点,并使用Cytoscape3.9.0软件进行药物-活性成分-靶点互作网络构建获取核心成分。通过String网站对药物-疾病共同靶点进行蛋白质-蛋白质相互作用分析得到核心靶点。使用Metascape平台对共同靶点进行GO及KEGG富集分析。最后运用AutoDock和PyMol软件对核心成分和核心靶点进行分子对接和可视化处理。结果:共获得药物活性成分7个,药物-疾病共同靶点139个。其中核心活性成分3个:槲皮素、木犀草素、山奈酚;核心靶点5个:TP53、AKT1、JUN、TNF、EGFR。GO分析得到2281个相关条目。KEGG分析得到326条信号通路。分子对接显示槲皮素、木犀草素、山奈酚与TP53、AKT1、JUN、TNF、EGFR之间均具有较强亲和力。结论:桔梗-鱼腥草药对可能通过TP53、AKT1、JUN、TNF、EGFR等靶点和癌症通路、PI3K-AKT信号通路等途径发挥抗NSCLC的作用。

Objective:To explore the mechanism of action of Platycodonis Radix and Houttuyniae Herba in the treatment of non-small cell lung cancer(NSCLC)through network pharmacology combined with GEO data mining and molecular docking technology.Methods:The active ingredients and targets of Platycodonis Radix and Houttuyniae Herba were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and disease-related targets were obtained from Gencards,OMIM and GEO databases.The common targets of Platycodonis Radix and Houttuyniae Herba and NSCLC were obtained by intersection of the two targets,and the drug active ingredient target interaction network was constructed by using Cytoscape 3.9.0 software to obtain core components.Obtain core targets through protein protein-interaction analysis of drug disease common targets through String Website.Conduct GO and KEGG enrichment analysis on common targets using the Metascape platform.Finally,AutoDock and PyMol software were used to perform molecular docking and visualization of core components and core targets.Results:Obtained a total of 7 active ingredients and 139 drug disease common targets.Among them,there were three core active ingredients:quercetin,luteolin and kaempferol.And 5 core targets:TP53,AKT1,JUN,TNF,EGFR.GO analysis yielded 2281 related items.KEGG analysis revealed 326 signal pathways.Molecular docking showed strong affinity between Quercetin,Luteolin and Kaempferol with TP53,AKT1,JUN,TNF and EGFR.Conclusion:Platycodonis Radix and Houttuyniae Herba may exert anti-NSCLC effects through targets such as TP53,AKT1,JUN,TNF,EGFR,as well as cancer pathways and PI3K-AKT signaling pathways.