基于网络药理学及分子对接探究扶正抗癌汤抑制卵巢癌的作用机制

Mechanism of Fuzheng Kangai Decotion(扶正抗癌汤)in treating Ovarian Carcinoma based on Network Pharmacology and Molecular Docking

目的基于网络药理学整合分子对接法探究扶正抗癌汤治疗卵巢癌(ovarian carcinoma,OC)的潜在作用机制。方法从TCMSP数据库筛选扶正抗癌汤的药物活性成分,并预测药物活性成分的潜在靶点;在GenCards数据库检索卵巢癌疾病相关靶点;利用R软件提取药物靶点与疾病靶点的交集基因集;利用String对药物与疾病靶点的交集基因集进行蛋白互做分析,并用Cytoscape进行Network Analyzer分析以获得扶正抗癌汤治疗卵巢癌的关键靶点;利用Metascape对关键靶点进行GO富集分析和KEGG通路富集分析;通过AutoDock软件对分析结果进行验证。结果共得出扶正抗癌汤活性成分174种,药物靶点285个,卵巢癌靶点1901个,最终得出关键靶点162个、KEGG通路196条。结果表明,扶正抗癌汤治疗卵巢癌主要成分为槲皮素、β-谷甾醇、柚皮素、黄芩素、川陈皮素等,这些有效成分通过调节TP53、AKT1、VEGFA、JUN等几种信号蛋白的功能来抑制卵巢癌细胞的生长和转移,这些信号蛋白调节涉及癌症的途径和TNF信号通路以及MAPK信号通路。预计扶正抗癌汤治疗卵巢癌主要涉及蛋白激酶结合、转录因子结合、蛋白激酶活性、蛋白质结构域特异性结合和核受体活性等分子功能。分子对接分析显示Stigmasterol与TP53、AKT1、VEGFA结合程度最高,baicalein与JUN结合程度最高,验证了扶正抗癌汤的有效成分可以调节核心靶点来抑制卵巢癌细胞的生长和转移。结论本研究初步探析了扶正抗癌汤通过调控基因表达治疗卵巢癌的机制,以期为OC的中西医结合治疗提供新思路。

Objective To explore the potential mechanism of Fuzheng Kangai Decotion(扶正抗癌汤)in the treatment of Ovarian Carcinoma(OC).Methods To screen the active ingredients of Fuzheng Kangai decoction from TCMSP database and predict the potential targets of active ingredients;to search the related targets of ovarian cancer in GenCards database;to extract the intersection gene set of drug targets and disease targets by R software;to analyze the protein interaction of the intersection gene set of drug and disease targets by string,and to conduct network analysis by Cytoscape Analyzer analysis was used to obtain the key targets of Fuzheng Kangai Decoction in the treatment of ovarian cancer;Metascape was used for go enrichment analysis and KEGG pathway enrichment analysis of key targets;AutoDock software was used to verify the analysis results.Results A total of 174 active components,285 drug targets and 1901 ovarian cancer targets were obtained.162 key targets and 196 KEGG pathways were finally obtained.The results showed that the main components of Fuzhenganticancer decoction in the treatment of ovarian cancer were quercetin,β-phytosterol,nelein,baicalein,citriletin,etc.These active components could inhibit the growth and metastasis of ovarian cancer cells by regulating the functions of TP53,Akt1,VEGFA,Jun and other signaling proteins.These signaling proteins regulate pathways involved in cancer and the TNF and MAPK signaling pathways.It is expected that the treatment of ovarian cancer by Fuzheng anticancer decoction mainly involves molecular functions such as protein kinase binding,transcription factor binding,protein kinase activity,protein domain specific binding and nuclear receptor activity.Molecular docking analysis showed that STIGmasterol had the highest binding degree with TP53,Akt1,and VEGFA,and baicalein had the highest binding degree with Jun,which verified that the active components of Fuzhenganticancer decoction could regulate the core targets to inhibit the growth and metastasis of ovarian cancer cells.Conclusion This study preliminarily explored the mechanism of Fuzheng Anti-cancer Decoction in treating ovarian cancer by regulating gene expression,in order to provide a new idea for the treatment of OC with integrated traditional Chinese and western medicine.