基于网络药理学研究黄酮类化合物治疗胃癌的作用机制

Study on the mechanism of flavonoids in the treatmentof gastric cancer based on network pharmacology

通过网络药理学方法分析从实验室提取的6个黄酮类化合物治疗胃癌的作用机制,通过SwissADME数据库分析6个黄酮类化合物的药代动力学参数并利用Swiss Target Prediction数据库预测其有效靶点,利用GeneCards数据库获得胃癌靶点,用Venn软件获取交集。通过String数据库获取蛋白互作网络信息,利用Cytoscape3.8.0软件进行PPI和化合物-疾病-靶点网络的可视化及分析,筛选黄酮类化合物治疗胃癌的关键靶点,用R语言进行GO功能、KEGG通路富集分析,最后利用AutoDock软件进行分子对接验证黄酮类化合物与PI3K-Akt通路相关蛋白的结合能力。从黄酮化合物中筛选出228个活性靶点,胃癌相关靶点12309个,交集靶点为203个。通过网络筛选了SRC、PIK3R1等10个核心靶点,通过富集分析共筛选出163个GO功能条目与156条KEGG信号通路,通过分子对接验证结合能力较好。黄酮类化合物具有多组分、多靶点、多途径、多通路治疗胃癌的特点,预测了黄酮类化合物抗胃癌的作用机制,为新药的研究开发提供思路与理论依据。

The mechanism of action of six flavonoids extracted from the laboratory in the treatment of gastric cancer was analyzed by network pharmacology method,the pharmacokinetic parameters of six flavonoids were analyzed by SwissADME database,and their effective targets were predicted by Swiss Target Prediction database,gastric cancer targets were obtained by GeneCards database,and intersections were obtained by Venn software.The information of protein interaction network was gotten through the String database,using the Cytoscape3.8.0 software to visualize and analyze PPI and compound-disease-target network,the key targets of flavonoids for the treatment of gastric cancer were screened.R language was used to conduct GO function and KEGG pathway enrichment analysis.Finally AutoDock software was used to conduct molecular docking to verify the binding ability of flavonoids and PI3K-Akt pathway related proteins.There were 228 active targets,12309 gastric cancer related targets and 203 cross targets screened from flavonoids.Ten core targets such as SRC and PIK3R1 were screened through the network,163 GO functional items and 156 KEGG signal pathways were screened through enrichment analysis,and the binding ability was verified to be good through molecular docking.Flavonoids have the characteristics of multi-component,multi-target and multi-pathway in the treatment of gastric cancer.The mechanism of flavonoids is predicted in the treatment of gastric cancer and this mechanism provides ideas and theoretical basis for the research and development of new drugs.