COX-2选择性抑制剂诱导人喉癌Hep-2细胞凋亡及自噬的体外研究  

COX-2 specific inhibitor induced apoptosis and autophagy in Hep-2 cells in vitro

作　　者：赵永强[1,2] 谢晓烨 陈雪梅[1] 冯慧伟[1] 贾涛[1] 张辉[1] 范献良[1] 

机构地区：[1]山东大学第二医院耳鼻咽喉一头颈外科,山东济南250033 [2]山东大学医学院,山东济南250012

出　　处：《山东大学学报（医学版）》2014年第9期39-43,共5页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金联合专项(ZR2013HL028)

摘　　要：目的：初步探讨环氧化酶-2（COX-2）选择性抑制剂塞来昔布对人喉癌Hep-2细胞诱导凋亡的作用及可能的机制并观察其引起的自噬现象。方法用四甲基偶氮唑盐（MTT）法，检测塞来昔布以不同浓度（0～100μmol/L）及作用时间（0～72 h）处理Hep-2细胞后细胞增殖活力的变化；流式细胞仪检测不同浓度及时间塞来昔布处理后Hep-2细胞的凋亡率；透射电镜观察塞来昔布处理后的细胞超微结构改变；Western blotting 检测凋亡诱导因子（AIF）移位改变。结果塞来昔布呈时间和浓度依赖性地抑制Hep-2细胞的增殖；诱导喉癌细胞凋亡并呈浓度依赖性；药物处理72 h与48 h相比凋亡率的改变无统计学意义（P＞0．05），药物处理72 h后在电镜下观察到自噬现象；AIF蛋白逐渐从线粒体释放、移位到细胞核。结论塞来昔布可诱导喉癌细胞凋亡，其机制涉及非caspase依赖的AIF机制，Hep-2细胞产生的自噬可能会对抗塞来昔布诱导的凋亡。Objective To investigate the ability of celecoxib inducing apoptosis in Hep-2 cells and its possible mecha-nisms,as well as to observe the autophagy of the cells.Methods MTT was used to observe the proliferation of Hep-2 cells treated with celecoxib at different doses（0-100μmol/L）and for different hours（0-72 hours）.Cell ultrastructure was observed by electron microscope.Hep-2 cells were treated with celecoxib at different doses and for different hours and then the cell apoptosis rate was measured by flow cytometry.AIF expression was examined by Western blotting. Results Celecoxib induced a time-and dose-dependent growth inhibition in Hep-2 cells.It also induced the apoptosis of Hep-2 cells in a dose-dependent manner.No significant difference existed in the apoptosis rate of the cells treated by celecoxib for 72 and 48 hours（P＆gt;0.05 ）.Autophagy was observed in Hep-2 cells treated by celscoxib for 72 hours. Celecoxib showed the ability of transporting AIF from mitochondria to cell nucleus.Conclusion Celecoxib can induce cell apoptosis,in which AIF mechanism may be involved.Autophagy induced by celecoxib may protect Hep-2 cells against apoptosis.

关 键 词：环氧化酶-2 塞来昔布 HEP-2细胞 凋亡 自噬 

分 类 号：R739.65[医药卫生—肿瘤]