基于网络药理学和分子对接探讨左金丸治疗肝癌的作用机制

Mechanism of action of Zuojin pills in treatment of liver cancer based on network pharmacology and molecular docking

目的:运用网络药理学和分子对接方法探讨左金丸治疗肝癌的作用机制。方法:从TCMSP和BATMAN-TCM数据库获取左金丸的化合物及其相应靶点,检索GeneCards、OMIM和TTD 3个数据库获得肝癌的相关靶基因,取两者靶基因交集得到左金丸治疗肝癌的预测靶基因;运用Cytoscape 3.7.1软件构建左金丸-化合物-靶点-肝癌和PPI网络图;运用R软件对预测靶基因进行GO和KEGG富集分析;最后运用分子对接技术对关键化合物和靶点进行验证。结果:共获取左金丸35个化合物及173个相应靶点,左金丸与肝癌的共同靶点有103个。PPI结果表明AKT1、MAPK1、TP53、JUN和RELA可能为左金丸治疗肝癌的关键靶点。富集分析示左金丸可能通过乙型肝炎、卡波西肉瘤相关疱疹病毒感染、人巨细胞病毒感染、丙型肝炎、MAPK信号通路、肝癌等信号通路抗肝癌。分子对接结果示槲皮素和黄连素均能与AKT1和MAPK1稳定结合。结论:本研究初步揭示了左金丸通过多成分、多靶点、多通路治疗肝癌的作用机制,为后续左金丸治疗肝癌提供理论参考。

Objective: To investigate the mechanism of action of Zuojin pills in the treatment of liver cancer based on network pharmacology and molecular docking.Methods: TCMSP and BATMAN-TCM databases were used to obtain the compounds of Zuojin pills and their corresponding targets, and GeneCards, OMIM,and TTD databases were searched to obtain the target genes associated with liver cancer;an intersection of the two was performed to obtain the predicted target genes of Zuojin pills in the treatment of liver cancer.Cytoscape 3.7.1 software was used to construct the Zuojin pills-compound-target-liver cancer network and the protein-protein interaction(PPI) network;R software was used to perform gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of predicted target genes;the molecular docking technique was used to validate the key compounds and targets.Results: A total of 35 compounds of Zuojin pills and 173 corresponding targets were obtained, and there were 103 common targets of Zuojin pills and liver cancer.The PPI network analysis showed that AKT1,MAPK1,TP53,JUN,and RELA might be the key targets of Zuojin pills in the treatment of liver cancer.Enrichment analyses showed that Zuojin pills exerted a therapeutic effect on liver cancer via multiple pathways including hepatitis B,Kaposi sarcoma-related Herpesvirus infection, human cytomegalovirus infection, hepatitis C,MAPK signaling pathway, and liver cancer signaling pathway.Molecular docking results showed that both quercetin and berberine could stably bind to AKT1 and MAPK1.Conclusion: This study reveals that Zuojin pills exert a therapeutic effect on liver cancer via multiple components, targets, and pathways, which provides a theoretical basis for subsequent studies on Zuojin pills in the treatment of liver cancer.