基于网络药理学探究“CRPC治疗方”治疗CRPC的作用机制

Exploring the mechanism of"CRPC therapeutic formula"in the treatment of CRPC based on network pharmacology

目的基于处方统计和网络药理学探究“CRPC治疗方”治疗去势抵抗性前列腺癌(CRPC)的作用机制。方法检索CNKI、万方、维普以及CBM数据库中收录的已公开发表的中医药治疗CRPC的个人医案,进行处方药味统计,依据频次取前十味药物,组方为“CRPC治疗方”;后通过TCMSP数据库收集“CRPC治疗方”活性成分,利用Swiss TargetPrediction数据库预测处方活性成分作用靶点;借助GeneCards、OMIM数据库收集疾病CRPC靶点;构建交集靶点Venny图,并利用Cytoscape 3.8.2构建“CRPC治疗方”治疗CRPC的“活性成分-基因靶点”网络图,利用String平台构建PPI网络,并利用Cytoscape 3.8.2的CytoNCA插件筛选关键靶点;采用Metascape平台进行GO富集分析以及KEGG通路分析。结果前十味药物为黄芪、熟地黄、茯苓、姜黄、白术、补骨脂、党参、炙甘草、白花蛇舌草、莪术,网络药理学筛选出“CRPC治疗方”活性成分157种及药物靶点136个,疾病靶点1396个,交集靶点99个,其中STAT3、c-jun、TP53、HIF1A、ESR1等为关键靶点,GO富集分析显示,主要涉及应答氧化应激、膜区、泛素-如蛋白质连接酶结合等,KEGG通路分析结果显示与PI3K-Akt信号通路、人巨细胞病毒感染、前列腺癌等148条通路有关。结论通过该研究可以发现“CRPC治疗方”通过多成分、多靶点、多通路治疗CRPC,这为后续进一步深入研究CRPC的治疗方法奠定相关基础。

Objective To explore the mechanism of"CRPC therapeutic formula"in the treatment of castrationresistant prostate cancer(CRPC)based on formula statistics and network pharmacology.Methods The published personal medical records of traditional Chinese medicine in the treatment of CRPC in CNKI,WanFang,VIP and CBM database were searched,and statistical analysis was conducted on herbal medicines in a formula.According to the frequency,the top ten herbal medicines were taken,which are composed of a"CRPC therapeutic formula"by compounding.After that,the active ingredients in the"CRPC therapeutic formula"were collected in TCMSP database,and the target of drug action of active ingredients in the formula was predicted by Swiss TargetPrediction database;CRPC disease targets were collected in GeneCards and OMIM databases;the Venny diagram of intersection targets was constructed,and Cytoscape 3.8.2 was utilized to construct the network diagram of"active ingredient-gene target"for the"CRPC therapeutic formula"to treat CRPC,the String platform was utilized to construct PPI network,and CytoNCA plug-in of Cytoscape 3.8.2 was utilized to screen key targets.The Metascape platform was used for GO enrichment analysis and KEGG pathway analysis.Results The top ten herbal medicines were Astragalus membranaceus,Rehmannia glutinosa,Poria cocos,Carcuma longa,Atractylodes macrocephala,Fructus Psoraleae,Radix Codonopsis,Radix Glycyrrhizae Preparata,Herba Hedyotis diffusae and Rhizoma Curcumae.157 kinds of active ingredients,136 drug targets,1396 disease targets and 99 intersection targets for"CRPC therapeutic formula"were screened out based on network pharmacology,of which STAT3,c-jun,TP53,HIF1A and ESR1 were the key targets.GO enrichment analysis showed that it mainly related to the response to oxidative stress,membrane domain,and ubiquitin,such as protein ligase binding,and KEGG pathway analysis showed that CRPC was related to 148 pathways,such as PI3K-Akt signaling pathway,human cytomegalovirus infection,prostate cancer and so on.Conclusion Through this study,it can be found that"CRPC therapeutic formula"can treat CRPC through multi-ingredient,multi-target and multi-pathway,which lays a relevant foundation for further research on the treatment of CRPC.