Nimesulide联合奥沙利铂对人肝癌细胞增殖与凋亡的影响  

Effects of Nimesulide combined with Oxaliplatin on the proliferation and apoptosis of human liver cancer cells

作　　者：刘利珍[1] 简捷[2] 吴建兵[1] 黄龙璋[1] 史芳[1] 

机构地区：[1]南昌大学第二附属医院肿瘤科江西省分子医学重点实验室,江西省南昌市330006 [2]南昌大学第二附属医院消化内科江西省分子医学重点实验室,江西省南昌市330006

出　　处：《世界华人消化杂志》2008年第36期4041-4045,共5页World Chinese Journal of Digestology

摘　　要：目的:探讨选择性环氧合酶-2(cyclooxy-genase-2,COX-2)抑制剂Nimesulide联合奥沙利铂(Oxaliplatin,L-OHP)对人肝癌细胞株SMMC-7721增殖与凋亡的影响,为肝癌的药物治疗提供依据.方法:预实验筛选Nimesulide有效终浓度与不同浓度L-OHP(0.5、1.0、2.0、5.0mg/L)联合处理肝癌细胞48h;另外选取L-OHP有效终浓度与Nimesulide筛选的浓度单独或联合处理肝癌细胞24h、48h、72h;采用倒置显微镜观察细胞形态学改变,四氮唑盐比色法(MTT法)观察细胞增殖活力的改变,流式细胞仪检测细胞凋亡率.结果:不同浓度Nimesulide及L-OHP对SMMC-7721表现出一定程度的生长抑制作用,并呈剂量依赖性.Nimesulide(50mmol/L)或L-OHP(1mg/L)单用时可显著抑制SMMC-7721细胞的增殖,选用Nimesulide 50mmol/L与L-OHP(0.5、1.0、2.0、5.0mg/L)联合使用时,联合抑制作用呈现协同作用(Q>1.15).L-OHP 1mg/L、Nimesulide 50mmol/L及两药联合处理SMMC-7721细胞24h、48h、72h,各处理组各时间点对肝癌细胞的抑制作用随着时间的延长而增大,并且两药联合作用有协同作用(Q>1.15).流式细胞仪检测分析发现两种药物均可有效诱导SMMC-7721细胞的凋亡,且在上述浓度联合应用时具协同效应.结论:Nimesulide与L-OHP对人肝癌细胞株SMMC-7721均有抑制增殖和促进凋亡作用,而且两者联合应用有协同作用.AIM： To investigate the effects of cycloxygenase-2 （COX-2） selective inhibitor Nimesulide combined with Oxaliplatin（L-OHP） on cell proliferation and apoptosis of human liver cancer cell line SMMC-7721. METHODS： Nimesulide at the effective final concentration determined by pre-screen test, combined with different concentrations of L-OHP （0.5, 1.0, 2.0, 5 mg/L） was used to treat liver cancer cells for 48 hours. L-OHP final concentration and the final concentration of Nimesulide alone or jointly were used to treat liver cancer cells 24 h, 48 h, 72 h. Cell morphology changes was detected using inverted microscopy; cell proliferation changes was determined using MTT; cell apoptosis was determined using flow cytometry. RESULTS： Nimesulide at different concentrations combined with L-OHP demonstrated growth inhibitory effect on SMMC-7721 with a dosage dependence effect. Nimesulide （50 μmol/L） or L-OHP （1 mg/L） alone significantly inhibited SMMC-7721 cell proliferation. The inhibitory effect of 50 μmol/L Nimesulide combined with L-OHP （0.5, 1.0, 2.0, 5.0 mg/L） was a joint synergy （Q 〉 1.15）. After SMMC-7721 cells were treated with L-OHP 1.0 mg/L, Nimesulide 50 μmol/L, alone or jointly at 24 h, 48 h, 72 h, inhibitory effect of liver cancer cells was increased with time and a synergic effect was observed （Q 〉 1.15）. Flow cytometry showed that both of the two drugs induced SMMC-7721 cells apoptosis, and the combined use resulted in synergic effect. CONCLUSION： Both Nimesulide and L-OHP can inhibit cell proliferation and promote cell apoptosis of human liver cancer cell line SMMC-7721, and combined use shows a syner gic effect.

关 键 词：NIMESULIDE 奥沙利铂 细胞增殖 凋亡 

分 类 号：R735.7[医药卫生—肿瘤] R733.71[医药卫生—临床医学]