塞来昔布对肝癌HepG2 HepG3细胞的免疫增敏作用

目的探讨选择性环氧合酶-2（COX-2）抑制剂塞来昔布（Celecoxib）对人肝癌HepG2和HepG3细胞株对肿瘤坏死因子相关的凋亡诱导配体（TRAIL）的增敏作用及其可能机制。方法以人HepG2 HepG3肝癌细胞为研究对象,以塞来昔布和TRAIL作为干预手段,采用四甲基偶氮唑蓝（MTT）法检测塞来昔布对肝癌细胞株的增殖抑制作用,采用流式细胞术,检测塞来昔布联合TRAIL对HepG2,HepG3细胞的凋亡及DR4,DR5的表达。塞来昔布与不同效靶比的细胞因子诱导的杀伤细胞（CIK）联合作用于人肝癌细胞株,经LDH检测法检测其杀伤作用。结果塞来昔布及TRAIL对人肝癌HepG2和HepG3细胞株均有显著抑制作用,塞来昔布联合TRAIL可显著增敏TRAIL对HepG2和HepG3的杀伤,其差异具有统计学意义（P〈0.05）,经过塞来昔布预处理的肝癌细胞更易被CIK细胞杀伤。结论塞来昔布对人肝癌HepG2和HepG3细胞株具有明显细胞毒性,联合TRAIL及CIK可显著增敏后者对肝癌细胞的杀伤效应,其机制可能与塞来昔布上调DR4,DR5有关。

Celecoxib sensitizes Hepatoma cells to immune-mediated cytotoxicity

Objective To investigate the effect of COX-2 inhibitor celecoxib on the growth of hepatic carcinoma HepG2 and HepG3 and explore its mechanism.Methods In human hepatic carcinoma cell line HepG2,HepG3 as the research object,using celecoxib and TRAIL as a means of intervention,the function of celecoxib on cell proliferation inhibition was observed in different concentration and time by MTT,by using flow cytometric technique for the observation of celecoxib combined with TRAIL on hepatoma cell apoptosis and express change of DR4 and DR5.The apoptosis effect of Celecoxib combined with different concentrations CIK cells on hepatoma cells was detected by LDH assay.Results Celecoxib and TRAIL has obvious inhibition effect on hepatic carcinoma cell line HepG2 and HepG3.Celecoxib would significantly sensitize TRAIL to HepG2 and HepG3,it has statistical significance（P 0.05）.Celecoxib pretreatment made hepatoma cells more susceptible to CIK cell killing.Conclusion Celecoxib has obviously cytotoxic on hepatic carcinoma cell line HepG2,HepG3.Celecoxib combine with TRAIL and CIK would significantly sensitize its cytotoxic effect.The mechanism may be associated with increased expression of DR4/5 by celecoxib pretreatment.