塞来昔布与阿霉素对Raji细胞增殖和凋亡的影响及机制

Effect of celecoxib and adriamycin on proliferation and apoptosis of Raji cells and its mechanism

目的:观察塞来昔布(celecoxib)单用及联合阿霉素(adriamycin,ADM)对Raji细胞增殖和凋亡的影响。方法:MTT法测塞来昔布单用或联合阿霉素干预后Raji细胞的增殖率;流式细胞技术检测细胞凋亡率;RT-PCR检测caspase-9mRNA变化;免疫组织化学法检测caspase-9蛋白的表达。结果:20～100μmol/L塞来昔布干预Raji细胞后,随药物浓度增高细胞增殖率减低,凋亡率增高(P<0.05)。联合阿霉素干预后细胞增殖率减低,凋亡率增高,与塞来昔布单用比差异有统计学意义(P<0.05);且伴随细胞caspase-9mRNA和蛋白的表达增高。结论:塞来昔布可抑制Raji细胞增殖,呈剂量和时间依赖;可诱导Raji细胞凋亡,伴有caspase-9的激活;塞来昔布联合小剂量阿霉素后以上作用增强。

Objective To assess the effect of celecoxib in combination with adriamycin（ADM） on cell proliferation and apoptosis. Methods Cell lines were treated with celecoxib,and cell proliferation was examined by the method of 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） at different time. The cellular apoptotic rate was analyzed by flow cytometry. RT-PCR was applied to distinguish the level of caspase-9 mRNA expression. Immunohistochemistry was used to detect the caspase-9 protein expression in Raji cells. Results Celecoxib inhibited the proliferation and increased the apoptosis of Raji cell lines in a dose-dependent and time-dependent manner within 20-100 μmol/L. Compared with the celecoxib alone,the proliferation of Raji cell lines incubated with celecoxib and adriamycin was decreased. Caspase-9 mRNA and protein expression in Raji cells were significantly enhanced after the treatment of celecoxib （P0.05）. Conclusion Celecoxib can inhibit the proliferation of Raji cells in a dose-dependent and time-dependent manner. Celecoxib may lead to the apoptosis of Raji cells by up-regulating activities of caspase-9. Adriamycin could intensify the effect.