基于网络药理学研究阿魏、九香虫治疗胃癌的作用机制

Study on the action mechanism of Ferula and Aspongopus chinensis Dallas in the treatment of gastric cancer based on network pharmacology

目的 通过网络药理学方法探讨阿魏、九香虫治疗胃癌的作用机制。方法 利用中药综合数据库(Traditional Chinese Medicines Integrated Database,TCMID)与文献检索获取阿魏、九香虫的活性成分,将化学活性成分导入PubChem统一格式。利用SwissTargetPrediction数据库预测活性成分靶点,利用比较毒物基因组学数据库(Compargtive Toxicogenomics Database,CTD)获取胃癌靶点,并与药物所对应的靶点比较,筛选出共同部分,然后采用Cytoscape3.8.0软件搭建“药物-成分-靶点-疾病”网络。通过String数据库获取共有靶点之间的相互作用关系,并筛选出关键靶点。将共有靶点导入注释、可视化和集成数据库(the Database for Annotation, Visualization and Integrated Discovery,DAVID)进行基因本体(gene ontology,GO)分析、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。结果 从阿魏中获得抗胃癌相关活性成分15个,九香虫21个,从阿魏、九香虫中发现共同作用于胃癌的靶点112个。获得丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)、蛋白激酶B1(protein kinase B1,AKT1)、热休克蛋白90α家族A类成员1(heat shock protein 90α family class A member 1,HSP90AA1)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、SRC基因等5个与胃癌相关的关键靶点,与胃癌密切联系的通路有磷脂酰肌醇3激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinase B,PI3K-Akt)信号通路、MAPK信号通路、细胞周期通路等。结论 阿魏、九香虫能够影响小血管生成,抑制细胞增殖、分化,促进细胞凋亡,可能通过抑制细胞周期G1期、G2/M期来发挥抗胃癌作用。

Objective To study the effect of Ferula and Aspongopus chinensis Dallas in the treatment of gastric cancer based on network pharmacology.Methods The chemical components of Ferula and Aspongopus chinensis Dallas were identified through literature and Traditional Chinese Medicine Ingredient Database(TCMID),which were input into PubChem Database and unified into a standard format.The human protein targets of the active components were predicted by using Swiss Target Prediction database.The targets of gastric cancer were obtained through Comparative Toxicogenomics Database(CTD)and compared with the corresponding targets of drugs to screen out the common parts,then Cytoscape3.8.0 software was used to construct drug-componenttarget-disease network diagram.The interaction relationship between common targets was obtained through String Database,and the key targets were screened out according to the interaction relationship.The common targets were input into The Database for Annotation,Visualization and Integrated Discovery(DAVID)Database for gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)analysis.Results 15 ferulic compounds and 21 ferulic compounds were respectively obtained,and a total of 112 gastric cancer targets were found.Five key targets related to gastric cancer were obtained,including mitogen-activated protein kinases(MAPK),protein kinase B1(AKT1),heat shock protein 90αfamily class A member 1(HSP90AA1),signal transducer and activator of transcription 3(STAT3)and SRC.The pathways closely related to gastric cancer were obtained,including phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt),mitogen-activated protein kinases(MAPK)and cell cycle pathways.Conclusion Ferula and Aspongopus chinensis Dallas can affect small angiogenesis,inhibit cell proliferation and differentiation,promote cell apoptosis,inhibit the G1 and G2/M phases of cell cycle to play an anti-gastric cancer effect.