基于网络药理学及生物信息学探讨藤梨汤治疗结直肠癌的作用机制研究

Study on the mechanism of action of Garcinia cambogia decoction in the treatment of colorectal cancer based on network pharmacology and bioinformatics

目的使用生物信息学技术和网络药理学探讨藤梨汤治疗结直肠癌(CRC)的潜在作用机制及对预后的影响。方法采用TCMSP和SymMap数据库检索藤梨汤的活性成分及靶点。通过GeneCards、TTD、OMIM、DisGeNET数据库等筛选CRC疾病靶点,并基于癌症基因组图谱计划数据库集筛选出CRC患者与健康人的差异基因。运用Venny 2.1平台获取藤梨汤与疾病的共有靶点,通过STRING数据库及Cytoscape 3.9.1构建蛋白质蛋白质相互作用(PPI)网络获得该网络核心靶点并构建“药物有效成分靶点作用通路”网络图。借助Metascape数据库对共有靶点进行GO及KEGG功能富集分析。结果获取藤梨汤中30个活性成分,药物靶点622个,疾病靶点27057个,“方病”关键靶点417个;藤梨汤治疗CRC的核心活性成分包括槲皮素、异鼠李素、信阳冬凌草甲素等;PPI网络中筛选前15个核心靶点有AKT1、STAT3、TP53、ESR1、MYC等。结论本研究初步揭示了藤梨汤治疗CRC的潜在作用机制及预后影响,表明该方治疗CRC具有多成分多靶点多通路的药效特点,并可能使患者生存获益,将为今后相关研究提供新思路和依据。

Objective To explore the potential mechanism of action and prognostic effects of Garcinia cambogia decoction in the treatment of colorectal cancer(CRC)using bioinformatics technology and network pharmacology.Methods TCMSP and SymMap databases were used to search the active ingredients and targets of Garcinia cambogia decoction.CRC disease targets were screened by GeneCards,TTD,OMIM,and DisGeNET databases,and differential genes between CRC patients and healthy individuals were screened based on The Cancer Genome Atlas database set.Venny 2.1 platform was used to obtain the common targets of Garcinia Cambogia decoction and disease,and protein-protein interaction(PPI)network was constructed through STRING database and Cytoscape 3.9.1 to obtain the core targets of this network and construct the network diagram of“drug-active ingredient-target-pathway of action”.GO and KEGG functional enrichment analyses of the common targets were performed with the help of Metascape database.Results A total of 30 active ingredients,622 drug targets,27057 disease targets and 417“prescription-disease”key targets were obtained from Garcinia cambogia decoction.The core active ingredients of Garcinia cambogia decoction for CRC include quercetin,isorhamnetin,oridonin,etc.The first 15 core targets screened in PPI network were AKT1,STAT3,TP53,ESR1,MYC,etc.Conclusion This study preliminarily revealed the potential mechanism of action and prognostic effects of Garcinia cambogia decoction in the treatment of CRC,indicating that this prescription has the pharmacodynamic characteristics of multi-component,multi-target and multi-pathway in the treatment of CRC,and may be beneficial to the survival of patients,which will provide new ideas and basis for future related studies.