基于网络药理学探讨八珍汤重塑食管癌肿瘤微环境的作用机制  

Study on the Mechanism of Bazhen Decoction in Remodeling Esophageal Cancer Tumor Microenvironment Based on Network Pharmacology

作　　者：瞿颖 向科旭 王蓓茹 侯铖宇 王继勇[3] QU Ying;XIANG Kexu;WANG Beiru;HOU Chengyu;WANG Jiyong(The First Clinical Medical School,Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510006,China;The First Affiliated Hospital of Hunan University of Medicine,Huaihua Hunan 418000,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510405,China)

机构地区：[1]广州中医药大学第一临床医学院,广东广州510006 [2]湖南医药学院第一附属医院,湖南怀化418000 [3]广州中医药大学第一附属医院,广东广州510405

出　　处：《新中医》2023年第24期119-128,共10页New Chinese Medicine

基　　金：国家中医药传承创新中心科研专项项目(2022ZD08)。

摘　　要：目的:基于网络药理学和生物信息学探讨八珍汤重塑食管癌肿瘤微环境的作用机制。方法:收集中药系统药理学数据库与分析平台(TCMSP)中八珍汤组方药物的有效成分及其靶点,从TCGA数据库下载食管癌患者的转录组数据和临床信息,根据ESTIMATE算法计算食管癌样本的基质评分、免疫评分、综合评分,筛选食管癌肿瘤微环境预后相关基因,将这些基因作为重塑食管癌肿瘤微环境的相关靶点。最后将中药靶点和疾病靶点取并集,获得八珍汤重塑食管癌肿瘤微环境的相关靶点,并通过Cytoscape 3.9.1构建“中药-成分-靶点”网络。基于STRING 11.5数据库及Cytoscape 3.9.1软件构建蛋白质-蛋白质相互作用(PPI)网络并通过Cytoscape 3.9.1的插件CytoHubba筛选核心基因,运用DAVID数据库对中药与疾病共有靶点进行基因本体(GO)富集分析以及京都基因与基因组百科全书(KEGG)通路分析,并对药物有效成分和核心基因进行分子对接验证。结果:获得八珍汤重塑食管癌肿瘤微环境的31个相关基因,根据MCC算法筛选得到前5个较为重要的基因:ICAM1、CCL2、CXCL10、STAT1、VCAM1。GO功能、KEGG通路富集分析结果显示,中药-疾病共有靶点基因主要富集于趋化因子信号通路、TNF信号通路、NF-κB信号通路等。分子对接结果显示,八珍汤药物主要有效成分和核心靶点蛋白有良好的结合力。结论:八珍汤可能通过靶向ICAM1、CCL2、CXCL10、STAT1、VCAM1等关键基因调控趋化因子、TNF、NF-κB等信号通路重塑食管癌肿瘤微环境,从而影响食管癌细胞生长、侵袭转移、血管生成、化学耐药等。Objective:To explore the mechanism of Bazhen Decotion in remodeling esophageal cancer tumor microenvironment based on network pharmacology and bioinformatics.Methods:The active ingredients and targets of Bazhen Decotion were collected from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),transcriptome data and clinical information of esophageal cancer patients were downloaded from the TCGA database,and stromal score,immune score and comprehensive score of esophageal cancer samples were calculated according to the ESTIMATE algorithm.To screen the genes related to the prognosis of esophageal cancer microenvironment,and use these genes as the relevant targets to reshape the esophageal cancer microenvironment.Finally,Chinese medicinals targets and disease targets were selected and combined to obtain the related targets of Bazhen Decoction in reshaping esophageal cancer microenvironment,and the "Chinese medicinals-ingredients-targets" network was constructed by Cytoscape 3.9.1.Construct protein-protein interaction(PPI) network based on STRING 11.5 database and Cytoscape 3.9.1 software,and screen core genes through CytoHubba,a plugin of Cytoscape 3.9.1.DAVID database was used to conduct gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis for common targets of TCM and diseases,and molecular docking verification of drug active ingredients and core genes was carried out.Results:A total of 31 genes related to the remodeling of esophageal cancer tumor microenvironment by Bazhen Decoction were obtained,and the top 5 important genes were selected according to MCC algorithm:ICAM1,CCL2,CXCL10,STAT1 and VCAM1.GO function and KEGG pathway enrichment analysis showed that the common target genes of Chinese medicinals-diseases were mainly enriched in chemokine signaling pathway,TNF signaling pathway,NF-κB signaling pathway and so on.The results of molecular docking showed that the main active components of Bazhen Decoction had good binding

关 键 词：食管癌 肿瘤微环境 八珍汤 生物信息学 网络药理学 分子对接技术 

分 类 号：R735.1[医药卫生—肿瘤]