目的:运用网络药理学分析四君子汤辅助治疗胃癌的作用机制,并进行分子对接验证.方法:通过中药系统药理学数据库和分析平台提取四君子汤中各药物化学成分及相关靶点,并利用常用疾病数据库筛选出胃癌靶点,绘制药物-疾病共同靶点的韦恩图.再用Cytoscape软件构建药物-疾病调控网络,在STRING数据库中构建药物-疾病共同靶点的蛋白质相互作用网络(protein-protein interaction,PPI),在Metascape数据库进行基因本体(gene ontology,GO)生物过程富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析.通过分子对接验证前期所得的关键药物化学成分与核心靶点的结合可能性.结果:得到四君子汤135个药物化学成分,胃癌作用靶点1423个,药物-疾病共同作用靶点65个;通过药物-疾病调控网络和拓扑分析,发现药物化学成分中度值较高的为槲皮素、山柰酚、异鼠李素等;PPI网络核心靶点为MAPK8、ESR1、CCND1等;GO富集分析显示,四君子汤主要通过影响细胞RNA聚合酶Ⅱ启动子转录的正调控、凋亡过程的负调控、DNA模板的转录正调控等发挥生物学和药理学的多种效应;相应的KEGG通路分析显著富集于癌症途径、p53信号通路、NF-κB信号通路等多条与胃癌密切相关的通路;分子对接验证结合性好.结论:网络药理学初步明确了四君子汤辅助治疗胃癌潜在的靶点通路机制,分子对接角度进一步验证了研究思路的正确性.
Analysis of the Mechanism of Ancient Formula Sijunzi Tang in the Adjuvant Treatment of Gastric Cancer Based on Network Pharmacology and Molecular Docking
Objective:To analyze the mechanism of action of Sijunzi Tang in the adjuvant treatment of gastric cancer using network pharmacology and to perform molecular docking verification.Methods:The chemical components and related targets of the drugs in Sijunzi Tang were extracted through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the targets of gastric cancer were screened using the database of common diseases,and the Venn diagram of drug-disease common targets was drawn.Cytoscape software was used to construct the drug-disease regulatory network,and the protein-protein interaction(PPI)network of drug-disease common targets was constructed in STRING database,and GO(Gene ontology)biological process enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed in Metascape database.The binding potential of the chemical ingredients of key medicine obtained in the preliminary stage to the core target was verified by molecular docking.Results:All 135 chemical components of Sijunzi Tang,1423 targets for gastric cancer,and 65 targets for drug-disease interaction were obtained;Through the drug disease regulation network and topology analysis,it was found that quercetin,kaempferol,and isorhamnosum have higher moderate values in the chemical composition of drugs;The core targets of PPI network are MAPK8,ESR1,CCND1,etc;GO enrichment analysis showed that Sijunzi Tang mainly exerts various biological and pharmacological effects by affecting the positive regulation of RNA polymerase Ⅱ promoter transcription,negative regulation of apoptosis process,and positive regulation of DNA template transcription;The corresponding KEGG pathway analysis is significantly enriched in the cancer pathway,p53 signaling pathway,and NF-κB signaling pathways closely related to gastric cancer;Molecular docking verification has good binding affinity.Conclusion:Network pharmacology has initially clarified the potential target pathway mechanism of Sijunzi Tang for the adjuvant treatment of gastric cancer,and the molecular docking has further verified the research idea.
NETL
NSTL
万方数据
维普
