塞来昔布抑制肝癌细胞株增殖及其机制的实验研究

Studies on celecoxib inducing hepatoma cell apoptosis and its mechanism

目的:研究特异性环氧化酶-2(COX-2)抑制剂塞来昔布对人肝癌细胞株SMMC-7721是否有抑制增殖、诱导凋亡作用并初步探讨其作用机制。方法:采用四氮唑盐比色法(MTT法)观察不同浓度的塞来昔布作用后细胞增殖活力改变;流式细胞仪检测细胞凋亡百分率及细胞周期变化;免疫组化观察Bcl-2蛋白和Bax蛋白表达情况。结果:MTT法显示随着塞来昔布浓度和作用时间增加,细胞增殖抑制率上升;流式细胞仪测定空白对照组未见明显凋亡峰,塞来昔布组出现凋亡峰,凋亡率随着时间及药物浓度变化而变化,二者呈正相关;免疫组化显示经塞来昔布干预后,凋亡蛋白Bax表达增加,而Bcl-2表达减少,并随时间和药物浓度变化而明显。结论:塞来昔布抑制SMMC-7721细胞增殖,促进SMMC-7721细胞凋亡,并呈剂量和时间依赖性。其作用机制之一可能是通过减少Bcl-2的表达,增加Bax的表达,从而启动细胞凋亡途径。

Objective：To investigate the effect and mechanism of a selective cyclooxygenase-2 inhibitor （celecoxib） on hepatoma cell line SMMC-7721 proliferation and apoptosis. Methods： MTT assay was used to study the inhibitive effect of celecoxib on the growth of hepatoma cell. The effect of celecoxib on cell cycle changes and apoptosis of cells was studied by flow cytometry（FCM）. The expression of Bax and Bcl-2 proteins were measured by immunohistochemistry. Results： MTT assay demonstrated that the increuse of inhibition rate on SMMC-7721 proliferation was associated with the increase of celecoxib concentration and exposure time. The celecoxib groups had apoptotic peaks, but not the control one. Besides, celecoxib decreased the expression of Bcl-2, but promoted the expression of Bax protein. Concluslon：The celecoxib inhibited the proliferation and induced the apoptosis of the SMMC-7721 cells in a dose- and time-dependent way. The possible mechanism may be via reducing the expression of Bcl-2, but increasing the level of Bax, through which induced the human hepatoma cell apoptosis by the mitochondria/Cyt C pathway.