Haloperidol可以增敏索拉非尼诱导的肝癌细胞铁死亡  

Haloperidol can sensitize sorafenib-induced iron death in hepatocellular carcinoma cells

作　　者：马凤娇 田国亮[1] 郭高生 陈雷[1] MA Feng-jiao;TIAN Guo-liang;GUO Gao-sheng;CHEN Lei(General Surgery,the People′s Liberation Army Joint Logistics Support Unit 981 Hospital,Chengde 067000,China)

机构地区：[1]中国人民解放军联勤保障部队第981医院普外科,河北承德067000

出　　处：《实用药物与临床》2021年第1期11-16,共6页Practical Pharmacy and Clinical Remedies

摘　　要：目的探讨haloperidol对肝癌细胞铁死亡进程的影响,为肝细胞癌的治疗提供新策略。方法索拉非尼处理肝癌细胞株HepG2,Huh-7,SMMC-7721和PLC/PRF/5,在体外构建铁死亡模型,利用CCK-8实验对细胞活性进行检测;用RT-qPCR实验以及Western-blot实验对SlR的mRNA水平及蛋白水平进行检测;向培养基中同时添加haloperidol和索拉非尼,利用CCK-8实验和克隆形成实验对细胞活性进行检测;最后,利用RT-qPCR实验以及Western-blot实验对铁死亡中相关分子GSH以及GPX4的变化进行进一步的检测。结果索拉非尼处理肝癌细胞株HepG2,Huh-7,SMMC-7721和PLC/PRF/5可以导致细胞铁死亡的发生,并且能够被铁死亡的特异性抑制剂Fer-1挽救;在索拉非尼诱导肝癌细胞发生铁死亡的过程中,SlR的表达升高,并且具有统计学意义;和索拉非尼组进行比较,haloperidol+索拉非尼组的细胞活性进一步降低且具有统计学意义;haloperidol能够进一步促进索拉非尼导致的GSH及GPX4表达减少并且具有统计学意义。结论Haloperidol促进索拉非尼导致的GSH及GPX4表达来促进肝癌细胞铁死亡进程,加快肝癌细胞死亡。Objective To investigate the effect of haoperidol on the ferroptosis process of hepatocellular carcinoma cells and to provide a new strategy for the treatment of hepatocellular carcinoma.Methods Sorafenib was used to treat hepatocellular carcinoma cell lines HepG2,Huh-7,SMMC-7721,and PLC/PRF/5,and an ferroptosis model in vitro was established,and CCK-8 assay was used to detect cell viability;RT-qPCR experiment and Western-blot were used to determine the mRNA and protein levels of SlR;haloperidol and sorafenib were added to the culture medium at the same time,and the cell viability was tested using CCK-8 and clone formation experiments;finally,RT-qPCR and Western-blot experiments were used to further detect the changes of related molecules GSH and GPX4 in ferroptosis.Results Sorafenib-treated hepatocellular carcinoma cell lines HepG2,Huh-7,SMMC-7721,and PLC/PRF/5 could cause ferroptosis in cells and could be rescued by Fer-1,a specific inhibitor of ferroptosis.In the process of ferroptosis induced by sorafenib in hepatocellular carcinoma cells,the expression of SlR increased and was statistically significant;compared with the sorafenib group,the cell activity of the haloperidol+sorafenib group was further reduced,which was statistically significant.Haloperidol could further promote the reduction of GSH and GPX4 expression caused by sorafenib,which had statistical significance.Conclusion Haloperidol promotes the expression of GSH and GPX4 caused by sorafenib in order to promote the ferroptosis process of hepatocellular carcinoma cells and accelerate the death of hepatocellular carcinoma cells.

关 键 词：肝细胞癌 索拉非尼 HALOPERIDOL 铁死亡 

分 类 号：R735.7[医药卫生—肿瘤]