基于网络药理学和分子对接探究安替可胶囊治疗肝癌的作用机制

To explore the mechanism of Antike capsule in treating liver cancer based on network pharmacology and molecular docking

目的基于网络药理学和分子对接探究安替可胶囊治疗肝癌的作用机制。方法使用TCMSP、SWISStarget、Uniprot数据库结合文献,查找安替可胶囊的作用化合物和化合物靶点。使用TCGA数据库获取肝癌疾病相关靶点。获得药物与疾病交集靶点,将其导入Cytoscape 3.8.2软件进行药物-靶点-疾病可视化网络图。对交集靶点进行PPI网络分析、极限乘积法生存分析、基因GO功能分析和KEGG通路分析,并将关键靶点进行分子对接。结果得到安替可胶囊靶点215个,肝癌靶点674个,其中交集靶点10个,其中CYP2C19、GCGR、ADCY1、DPP4表达与肝癌病死率呈负相关;AURKA、NUDT1、CDK1、AURKB、G6PD表达与肝癌病死率呈正相关。富集分析发现,10个关键靶点与19个生物学过程相关,与8个细胞组成相关,与6个组织学功能和2条信号通路相关。分子对接显示,G6PD是化合物作用最多的靶点,其次是AURKA;PARP1是结合能最好的靶点,其次是AURKA。结论安替可胶囊可能作用于CYP2C19、GCGR、ADCY1、AURKA、PARP1、NUDT1、CDK1、AURKB、DPP4、G6PD等多途径治疗肝癌,为进一步研究其药效作用机制奠定基础。

Aim To explore the mechanism of Antike capsule in the treatment of hepatocellular carcinoma based on network pharmacology and molecular docking.Methods TCMSP,SWISStarget and Uniprot databases were used to search the active compounds and compound targets of Antike capsules.The target of liver cancer disease was obtained by using TCGA database.The drug and disease intersection targets were obtained and imported into Cytoscape 3.8.2 software for drug-target-disease visualization network diagram.PPI interaction analysis,survival analysis by limit product method,gene GO function analysis and KEGG pathway analysis were performed for intersection targets,and molecular docking was performed for key targets.Results 215 targets of Antike capsule and 674 targets of liver cancer were obtained,including 10 intersection targets.The expressions of CYP2C19,GCGR,ADCY1 and DPP4 were negatively correlated with the mortality of liver cancer.The expressions of AURKA,NUDT1,CDK1,A URKB and G6PD were positively correlated with the mortality of liver cancer.Enrichment analysis found that 10 key targets were associated with 19 biological processes,8 cell compositions,6 organizational functions,and 2 signaling pathways.Molecular docking showed that G6PD was the most active target,followed by AURKA.PARP1 was the best binding energy target,followed by A URKA.Conclusion Antike capsule may have effects on CYP2C19,GCGR,ADCY1,AURKA,PARP1,NUDT1,CDK1,AURKB,DPP4,G6PD and other multi-channel treatment for liver cancer,which provides a foundation for further study of its pharmacological mechanism.