基于网络药理学探讨豆甾醇抗胃癌的靶点与机制

Study on anti-gastric cancer mechanism of stigmasterol based on network pharmacology

豆甾醇是来源于食物中的一种植物不饱和甾醇,在胃癌防治中展现出良好的应用前景。基于网络药理学探讨豆甾醇抗胃癌的作用靶点及分子机制。借助PharmMapper数据库得到药物相关靶点,通过疾病数据库Genecard和OMIM(Online Mendelian Inheritance in Man)获得胃癌相关靶点;对潜在标靶进行GO(Gene Ontology)、KEGG(Kyoto Encyclopedia of Genes and Genomes)富集分析得到相关作用通路;随后,利用STRING数据库分析治疗靶点之间蛋白的相互作用,借助Cytoscape3.8.0中CytoHubba插件构建蛋白质相互作用网络以获得Hub基因,预测豆甾醇抗胃癌的作用靶点及机制。借助数据库得到豆甾醇潜在胃癌治疗靶点19个,涉及77个生物过程与10条信号通路;通过蛋白互作网络取排名前5的Hub基因,分别为TERT、MET、SRC、MDM2、HIF1A。结果显示,网络药理学可以准确预测豆甾醇抗胃癌的作用靶点并揭示其分子机制与PI3K(Phosphatidylinositide 3-kinases)/AKT(蛋白激酶B)和RAS(Rat Sarcoma)通路上TERT、MET、SRC、MDM2、HIF1A这些关键基因的表达有关。

Stigmasterol is a kind of plant unsaturated sterol from food,which shows good application prospect in the prevention and treatment of gastric cancer.Based on network pharmacology,this study investigated the target and molecular mechanism of stigmasterol against gastric cancer.Drug related targets were obtained by PharmMapper database,and gastric cancer related targets were obtained by Genecard and OMIM(Online Mendelian Inheritance in Man)disease databases.GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)enrichment analysis of potential targets were performed to obtain the relevant action pathways.Then,STRING database was used to analyze the protein interaction between treatment targets,and the protein interaction network was constructed with CytoHubba plug-in in Cytoscape3.8.0 to obtain Hub genes,to predict the target and mechanism of stigmasterol against gastric cancer.19 potential therapeutic targets of stigmasterol for gastric cancer were obtained by database.Then GO and KEGG enrichment analysis was performed on 19 therapeutic targets to obtain 77 biological processes and 10 signaling pathways.The top 5 Hub genes were selected through the protein interaction network,which were TERT,MET,SRC,MDM2 and HIF1A.The results showed that the Hub genes were closely related to the prevention and treatment of gastric cancer.Conclusions:Network pharmacology can accurately predict the anti-gastric cancer target of stigmasterol and reveal its molecular mechanism related to the expression of key target genes such as TERT,MET,SRC,MDM2 and HIF1A in PI3K/AKT and RAS pathways.