基于网络药理学探讨通幽汤治疗食管癌的作用机制  

Exploration of Therapeutic Mechanism of Tongyou Decoction for Esophageal Cancer Based on Network Pharmacology

作　　者：孙亚云 王若凡 张娟[1,2] SUN Ya-yun;WANG Ruo-fan;ZHANG Juan(Henan University of Chinese Medicine,Zhengzhou 450046 Henan,China;Henan Provincial Hospital of Traditional Chinese Medicine,Zhengzhou 450002 Henan,China)

机构地区：[1]河南中医药大学,河南郑州450046 [2]河南省中医院,河南郑州450002

出　　处：《中医肿瘤学杂志》2020年第3期49-59,共11页Journal of Oncology in Chinese Medicine

基　　金：国家中医临床研究基地科研专项(编号:2019JDZX028);国家中医临床研究基地科研专项(编号:2019JDZX034);国家中医临床研究基地科研专项(编号:2019JDZX053)。

摘　　要：目的运用网络药理学的方法探讨通幽汤治疗食管癌的作用机制。方法通过中药系统药理学数据库分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、中医药综合数据库(Traditional Chinese Medicine Integrative Database,TCMID)、中药分子机制的生物信息学分析工具(Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine,BATMAN-TCM)结合文献查找检索通幽汤的活性化学成分及其相应靶点,建立“药物-成分-靶点”数据信息库,采用Cytoscape3.7.2软件构建通幽汤“中药-活性成分-预测靶点”网络;通过人类基因信息网站(Genecards)、在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man,OMIM)、治疗靶标数据库(Therapeutic Target Database,TTD)、生物信息学和化学信息学数据库(DRUGBANK)获取食管癌相关疾病靶点;通过FUNRICH3.1.3将药物靶点与疾病靶点进行基因映射;通过String平台获取蛋白相互作用信息,构建蛋白互作网络(Protein-Protein Interaction,PPI)并挖掘网络中潜在的蛋白质功能模块;通过Metascape平台分析其参与的生物过程及信号通路,采用Cytoscape3.7.2软件构建“通幽汤成分-食管癌靶点-通路”网络;通过KM-plotter平台进行基因预后分析、GEPIA平台进行核心基因在食管癌癌组织和癌旁组织的差异验证。结果共获得161个化合物,251个药物靶点,1378个食管癌疾病靶点;基因映射后获得130个共同表达的基因;通幽汤治疗食管癌的核心活性成分为槲皮素、山柰酚、木犀草素、β-谷甾醇等;核心靶点为PTGS2、HSP90AA1、PPARG、AR等;生物学通路主要作用于癌症通路、糖尿病并发症中的AGE-RAGE信号通路、前列腺癌通路等;KM-plotter分析显示HSP90AA1、CDK2、AKT1、JUN与食管腺癌总生存期相关,GSK3B、CHEK1、BCL2与食管鳞癌总生存期相关。GEPIA进一步分析示HSP90AA1、GSK3B、CHEK1在食管癌组织中的表达�Objective To explore the mechanism of Tongyou Decoction for the treatment of esophageal cancer by means of network pharmacology.Methods The active chemical components and their corresponding targets of Tongyou Decoction were searched through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Integrative Database(TCMID),and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM)combined with literature retrieval.The data information base of“drug-component-target”was established,and the network of“Chinese medicine-component-predicted target”for Tongyou Decoction was constructed by Cytoscape3.7.2 software.By using Genecards,Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),and DRUGBANK database,we obtained the esophageal cancer related disease targets.Gene mapping of drug targets and disease targets was achieved by FUNRICH3.1.3,and we obtained protein interaction information through String platform,constructed Protein-Protein Interaction(PPI)network and mined the potential protein functional modules in the network.Metascape platform was used to analyze the biological processes and pathways involved,and Cytoscape 3.7.2 software was used to construct the“Tongyou Decoction component-esophageal cancer target-pathway”network.The prognosis was analyzed by KM-plotter platform,and the differences of core genes in esophageal cancer tissues and their adjacent tissues were verified by GEPIA platform.Results A total of 161 compounds,251 drug targets and 1378 esophageal cancer related targets were obtained.After gene mapping,130 co-expressed genes were obtained.The core active ingredients of Tongyou Decoction for the treatment of esophageal cancer were quercetin,kaempferol,luteolin,beta-sitosterol,etc.The core targets include PTGS2,HSP90AA1,PPARG,AR,etc.Biological pathway mainly involve the cancer pathway,AGE-RAGE signaling pathway of diabetic complications,prostatic cancer pathway,etc.K

关 键 词：通幽汤 食管癌 网络药理学 成分 靶点 通路 

分 类 号：R730.52[医药卫生—肿瘤]