匹伐他汀治疗肝细胞癌机制的网络药理学研究  

Study on the mechanism of Pitavastatin treatment for hepatocellular carcinoma based on Network pharmacology

作　　者：梁中旭 蒋学华[1] 王三凌 LIANG Zhongxu;JIANG Xuehua;WANG Ling(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2024年第6期681-684,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的通过网络药理学、分子对接及体外细胞实验验证匹伐他汀治疗肝细胞癌的药效及其分子机制。方法使用PharmMapper网站预测匹伐他汀的作用靶点。通过GeneCards、OMIM及DisGeNet数据库获得肝细胞癌的潜在靶点采用STRING数据库获得匹伐他汀与肝细胞癌交集靶点的蛋白相互作用网络(PPI),并通过Cytoscape软件筛选关键靶点。使用分子对接评估匹伐他汀与关键靶点间的亲和力。在体外肝癌细胞系中验证匹伐他汀对细胞存活率的影响。结果共筛选得到匹伐他汀靶点286个,肝细胞癌靶点609个,二者交集靶点37个。通过PPI共筛选得到ECFR、ALB、HSP90AA1靶点。匹伐他汀与3个关键靶点均有较强的亲和力。40μmol·L^(-1)匹伐他汀处理24h可抑制HepC2肿瘤细胞的生长。结论匹伐他汀具一定的抗肝癌作用,可能与调控ECFR、ALB、HSP90AA1多种靶点有关。OBJECTIVE To validate the efficacy of Pitavastatin in treating hepatocellular carcinoma and its molecular mechanism through Network pharmacology,molecular docking,and experiment on cells in vitro.METHODS Targets of Pitavastatin were predicted using PharmMapper.The potential targets of hepatocellular carcinoma were obtained from GeneCards,OMIM,and DisGeNet databases.The STRING database was used to obtain protein-protein interaction networks(PPI)of intersecting targets between Pitavastatin and hepatocellular carcinoma,and Cytoscape was used to obtain key targets from PPI.The affinity between Pitavastatin and the key targets was assessed using molecular docking.Finally,the effect of Pitavastatin on hepatocellular carcinoma was verified in HepG2 cells in vitro.RESULTSSA total of 289 Pitavastatin targets,609 hepatocellular carcinoma targets,and 37 intersecting targets were screened.Three key targets including EGFR,ALB,and HSP90AA1 were identified by PPI.Pitavastatin had a strong affinity with the three key targets.40μmol·L^(-1)Pitavastatin treatment for 24 h could inhibit the growth of HepG2 cells.CONCLUSION Pitavastatin has certain anti-hepatocellular carcinoma effects,and the mechanism may be related to EGFR,ALB,and HSP9OAA1.

关 键 词：匹伐他汀 肝细胞癌 网络药理学 分子对接 细胞实验 表皮生长因子受体 白蛋白 热休克蛋白 

分 类 号：R96[医药卫生—药理学]