Celecoxib可通过抑制核转录因子-κB活性诱导SGC7901/ADR细胞的凋亡  

Celecoxib-induced apoptosis of gastric cancer cell line SGC7901/ADR by inhibiting nuclear factor-κB activity

作　　者：周洁[1] 陈虎[2] 郑海[2] 陈道达[2] 蒋春舫[2] 陈庆[2] 

机构地区：[1]华中科技大学同济医学院基础医学院生物化学与分子生物学教研室,武汉430030 [2]华中科技大学同济医学院附属协和医院外科

出　　处：《中华实验外科杂志》2010年第9期1269-1271,共3页Chinese Journal of Experimental Surgery

基　　金：湖北省自然科学基金资助项目（2007ABA065）;湖北省卫生厅科技攻关计划资助项目（JX1B006）

摘　　要：目的 观察环氧合酶-2（COX-2）特异性抑制剂Celecoxib对胃癌SGC7901/ADR细胞多药耐药1（mdr1）基因表达、核转录因子（NF）-κB激活水平及细胞凋亡的作用.方法 实验分为4组：SGC7901组、SGC7901＋Celecoxib组、SGC7901/ADR组和SGC7901/ADR＋Celecoxib组.逆转录-聚合酶链反应（RT-PCR）和流式细胞术检测mdr1基因的表达,电泳迁移率实验（EMSA）测定NF-κB激活水平,流式细胞术检测细胞内Rh123聚集及细胞凋亡.结果 SGC7901/ADR细胞中mdr1基因表达和NF-κB活性分别为SGC7901组的2.4倍和3.2倍（P＜0.01）,Celecoxib可显著抑制SGC7901和SGC7901/ADR细胞mdr1基因的表达及NF-κB活性,使SGC7901和SGC7901/ADR细胞内Rh123的聚集分别增加1.2倍和1.9倍,可使ADR诱导的SGC7901和SGC7901/ADR细胞的凋亡率分别提高1.65倍和2.98倍.结论 Celecoxib可能通过抑制NF-κB活性而抑制mdr1基因的表达,进而增加SGC7901/ADR细胞内药物聚集并促进细胞凋亡.Objective To investigate the effects of celecoxib on mdr1 expression, nuclear factorκB （NF-KB） activity and apoptosis of SGC7901/ADR. Methods Cultured SGC7901 cells were divided into four groups： SGC7901 group, SGC7901 ＋ ceIecoxib group, SGC7901/ADR group and SGC79OI/ADR ＋ celecoxib group. The expression of mdrl gene was detected by reverse transcription-polymerase chain reaction （RT-PCR） and flow cytometry. Electrophoretic mobility shift assay （EMSA） was used to measure the activity of NF-κB. Intracellular accumulation of Rh123 and apoptosis rate were measured by flow cytometry. Results The mdr1 gene expression and NF-κB activity were increased to 2. 4 fold and 3.2 fold respectively in SGC7901/ADR group as compared with SGC7901 group （P 〈0. 01 ）. Celecoxib inhibited the mdrl expression and NF-KB activity in SGC7901 and SGC7901/ADR groups. Celecoxib also improved the intracellular accumulation of Rh123 in SGC7901 group （1.2-fold） and SGC7901/ADR group （1.9-fold）.Celecoxib increased the apoptosis rate in SGC7901 group （1.65-fold） and SGC7901/ADR group （2. 98-fold）.induced by ADR. Conclusion Celecoxib can inhibit the mdr1 expression and increase intracellular Rh123 accumulation by suppressing NF-κB activity and induce the apoptosis of SGC7901/ADR cells.

关 键 词：CELECOXIB 核转录因子ΚB 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]