基于网络药理学和分子对接探讨膈下逐瘀汤治疗胃癌作用机制

Study on the Mechanism of Gexia Zhuyu Decoction in Treating Gastric Cancer Based on Network Pharmacology

目的基于网络药理学和分子对接探讨膈下逐瘀汤治疗胃癌的作用机制。方法利用TCMSP、化学专业数据库筛选膈下逐瘀汤所有药物的有效活性成分及相关靶点,采用GeneCards、OMIM数据库筛选胃癌的作用靶点,将其与药物的有效活性成分及相关靶点取交集,筛选疾病-药物的共同靶点。将筛选出的共同靶点在STRING数据库中构建蛋白相互作用网络,利用Cytoscape3.9.1软件绘制药物活性成分-靶点网络,运用R4.2.1软件对潜在作用靶点进行GO和KEGG富集分析,运用AutoDockTools-1.5.7软件将膈下逐瘀汤治疗胃癌的关键活性成分与核心靶点进行分子对接。结果获得药物活性成分173个(槲皮素、山柰酚、木犀草素、β-谷甾醇、黄芩素、柚皮素、柱头甾醇、异鼠李素等),胃癌作用靶点1463个,药物-疾病共同靶点139个(TP53、AKT1、ESR1、VEGFA、MYC、CTNNB1、TNF等)。根据GO、KEGG富集分析显示这些靶点主要富集在细胞凋亡、PI3K-Akt、TNF、IL-17、AGE-RAGE等信号通路上。分子对接结果显示膈下逐瘀汤的关键活性成分均能与胃癌的核心靶点产生稳定的结合。结论膈下逐瘀汤可能通过PI3K-Akt、TNF、IL-17及AGE-RAGE等信号通路诱导细胞凋亡发挥抗胃癌作用。

Objective To explore the mechanism of Gexia Zhuyu Decoction in treating gastric cancer based on network pharmacology and molecular docking technology.Methods TCMSP and chemical database were used to screen the effective active components and related targets of all drugs of Gexia Zhuyu Decoction.GeneCards and OMIM databases were used to screen the action targets of gastric cancer,and the effective active components and related targets of drugs were intersected to screen the common target of disease drug to screen disease-drug common targets.The screened common targets were used to construct protein interaction network in STRING database.The active components-target network of drugs was drawn using the software Cytoscape 3.9.1,and the GO and KEGG enrichment analysis of potential action targets was carried out using the software R4.2.1.AutoDockTools-1.5.7 software was used to dock the key active components of Gexia Zhuyu Decoction in the treatment of gastric cancer with the core targets.Results Totally 173 active components(quercetin,kaempferol,luteolinβ-Sitosterol,baicalein,naringenin,stigmasterol,isorhamnetin,etc.),1463 targets for gastric cancer,and 139 common drug disease targets(TP53,AKT1,ESR1,VEGFA,MYC,CTNNB1,TNF,etc.)were obtained.According to the enrichment analysis of GO and KEGG,these targets were mainly enriched in the signal pathways of cell apoptosis,PI3K-Akt,TNF,IL-17,AGE-RAGE,etc.;the results of molecular docking showed that the key active components of Gexia Zhuyu Decoction could stably combine with the core target of gastric cancer.Conclusions Gexia Zhuyu Decoction mainly plays an anti-gastric cancer role by inducing apoptosis through PI3K-Akt,TNF,IL-17 and AGERAGE signal pathways.