基于中医数据挖掘探讨桃红四物汤治疗结肠癌机制网络药理学研究

Network Pharmacology Study on the Mechanism of Taohong Siwu Decoction(桃红四物汤) in the Treatment of Colon Cancer Based on Data Mining of Traditional Chinese Medicine

目的通过网络药理学方法挖掘并研究桃红四物汤治疗结肠癌的化学基础和分子作用机制。方法根据组成桃红四物汤的6味药物为关键词,分别输入TCMSP数据库与TCMID数据库进行检索,筛选药物活性成分;通过UniProt规范化配对耙点名称;以“Colon Cancer”为检索词,在数据库DisGeNET以及OMIM检索结肠癌对应基因靶点;通过Venny 2.1得到药物有效活性成分调控结肠癌的靶点基因;将靶点基因导入到STRING,获得PPI互作图,Cytoscape绘制桃红四物汤有效成分-结肠癌-靶点基因-作用通路的网络图并进行分析,根据节点确定核心蛋白,导入DAVID,获得GO与KEGG并完成富集分析。将作用靶点导入KEGG,得出KEGG信号图并进行分析,探讨桃红四物汤治疗结肠癌的作用靶点及相关通路信息,预测治疗结肠癌的机制。结果检索出桃红四物汤61种活性成分,对应的药物基因223个,结肠癌基因靶点为161个。整理得到桃红四物汤有效成分与结肠癌靶基因的共同靶点为46个,挑选出药物有效成分为31个,通过PPI蛋白互作网络分析及有效成分-结肠癌-基因靶点-通路网络结构分析得出,其药物作用核心靶点为PTGS2、HSP90AA1、AKT1、TNF、TP53。获得GO过程122条,KEGG通路生物信息为85条。结论桃红四物汤通过癌症通路癌、症蛋白聚糖、癌症通路、大肠癌、PI3K-AKT信号通路、TNF信号通路、Micro RNA等通路作用于PTGS2、HSP90AA1、AKT1、TNF、TP53等核心靶点治疗结肠癌,其中癌症通路所包含的桃红四物汤的核心靶点基因计数及占比最多,被认为核心通路,通过数据挖掘出桃红四物汤治疗结肠癌的潜在的有效成分、靶点基因、生物过程及信号通路及其治疗其他恶性肿瘤及传染病的潜在价值,为下一步研究提供依据。

Objective Study and mining the chemical basis and molecular mechanism of Taohong Siwu Decoction(桃红四物汤)in the treatment of colon cancer through network pharmacology.Methods According to the six drugs that make up Taohong Siwu Decoction as keywords,enter the TCMSP and TCMID to search and screen the active ingredients of the drugs.Standardization of matching human gene target names through Uni Prot.Using“colon cancer”as the search term,search the corresponding gene targets of colon cancer in Dis Ge NET and OMIM.Through Venny2.1,the effective active ingredients of the drug are used to regulate the target genes of colon cancer.The common target is imported into STRING,and the PPI interaction network diagram is obtained.The effective component of Taohong Siwu Decoction-colon cancer-regulatory target-action pathway network is constructed and analyzed by Cytoscape software,in order to determine the core protein according to the node.Import the target gene data into DAVID to obtain the biological information of GO and KEGG for enrichment analysis.Introduce the target gene into KEGG,analyze the signal pathway diagram,and explore the target of Taohong Siwu Decoction in the treatment of colon cancer and related signal pathways.In order to analyze the mechanism of action of Taohong Siwu Decoction in the treatment of colon cancer.Results 61 active ingredients of Taohong Siwu Decoction were retrieved,corresponding to 223 drug genes,and 161 colon cancer gene targets.Through sorting out,the common targets of the effective ingredients of Taohong Siwu Decoction and the target genes of colon cancer are 46,and 31 active ingredients of the medicine are selected.Through the analysis of the PPI protein interaction network and the analysis of the effective component-colon cancer-gene target-pathway network structure.The core target of its drug action is PTGS2,HSP90 AA1,AKT1,TNF,TP53.122 paths of GO entries were obtained,KEGG was 85 paths.There were 85 paths of KEGG.Conclusion Taohong Siwu Decoction acts on PTGS2,HSP90 AA1,AKT1,TNF,TP53 and other core targets to treat colon cancer through multiple pathways such as pathways in cancer,proteoglycans in cancer,colorectal cancer,PI3 KAkt signaling pathway,TNF signaling pathway,and Micro RNAs in cancer,etc.Among them,the core target gene count and proportion of Taohong Siwu Decoction contained in the cancer pathway are the largest.It is considered the core channel.Through data mining,the potential effective ingredients,target genes,biological processes and signal pathways of Taohong Siwu Decoction in the treatment of colon cancer,as well as its potential value in the treatment of other malignant tumors and infectious diseases,provide a basis for further research.