基于网络药理学研究芹菜素治疗甲状腺癌的潜在靶点

Network pharmacology-based strategy for predicting therapy targets of apigenin on thyroid carcinoma

目的:应用网络药理学方法探究芹菜素治疗甲状腺癌的潜在靶点。方法:通过HIT、Binding Datebase、SEA、STITCH、PharmMapper筛选出芹菜素的靶点。挖掘TTD、DrugBank、CTD、DisGeNET数据库中与甲状腺癌的相关靶点。采用STRING数据库和Cytoscape3.2.1识别并筛选出芹菜素作用于甲状腺癌的关键基因。使用DAVID数据库对关键基因进行GO富集及KEGG信号通路富集分析。最后运用Kaplan-Meier Plotter数据库分析关键基因的预后。结果:纳入研究芹菜素175个靶点,甲状腺癌168个靶点。共同作用的靶点有37个。利用网络拓扑分析最终筛选出32个关键基因。芹菜素治疗甲状腺癌主要涉及HIF-1信号通路、癌症通路等通路。最后筛选出8个基因的表达与甲状腺癌患者生存预后相关。结论:ALB、CCNA2、CCND1、CYP2C19、TERT、TTR、BCL2、CBR1可能是芹菜素治疗甲状腺癌的潜在靶点。

Objective:To explore the potential therapeutic targets of apigenin in the treatment of thyroid carcinoma by network pharmacology.Methods:The targets of apigenin were screened by HIT(High Throughput),Binding Database,SEA(Similarity Ensemble Approach),STITCH(Search Tool for Interactions of Chemicals),PharmMapper.Thyroid carcinoma related targets were mined from TTD(Therapeutic Target Database),DrugBank,CTD(Comparative Toxicogenomics Database),DisGeNET databases.The String database and Cytoscape 3.2.1 software were used to identify and screen out the hub targets of apigenin for thyroid carcinoma.The David database was used for Gene Ontology(GO)enrichment and KEGG signal pathway enrichment analysis of hub targets.Finally,the Kaplan-Meier Plotter database was used to analyze the prognosis of hub targets.Results:175potential targets of apigenin and 168 potential targets related to thyroid carcinoma were included.37 overlapping targets of apigenin and thyroid carcinoma were obtained.32 hub targets were finally selected by network topology analysis.These hub targets of apigenin in the treatment of thyroid carcinoma were mainly enriched in involving HIF-1 signaling pathway,path-ways in cancer,etc.Finally,8 targets were screened to be associated with the survival and prog-nosis of thyroid carcinoma patients.Conclusion:Our study suggested that ALB,CCNA2,CCND1,CYP2C19,TERT,TTR,BCL2,CBR1 might be potential therapeutic targets for apigenin in the treatment of thyroid carcinoma.