三氧化二砷联合塞来昔布对上皮性卵巢癌细胞的抗肿瘤效应及相关机制研究

Combination of Arsenic Trioxide and Celecoxib: Anti- tumor activity on epithelial ovarian cancer cell line and the mechanisms

目的:研究对上皮性卵巢癌采用三氧化二砷(Arsenic Trioxide,AS2O3)与环氧化酶-2(Cyclooxygenase-2,COX-2)抑制剂塞来昔布(Celecoxib)联合用药的有效性及其机制。方法:以上皮性卵巢癌细胞株OVCAR-3为研究对象,采用MTT体外药敏试验、Hoechest33258凋亡染色、流式细胞仪检测凋亡及细胞周期、蛋白质印迹法检测环氧化酶-2、凋亡相关蛋白等方法在细胞水平检验AS2O3和Celecoxib的单药及联合用药的有效性及可能的分子机制。结果:AS2O3和Celecoxib对OVCAR-3细胞株均具有剂量依赖性的生长抑制作用,两种药物单药的IC50值分别为4.72μmol/L和42.58μmol/L。两药联合后呈现明显的协同抗肿瘤效应,联合后的增殖抑制率和细胞凋亡率均大于任一单药作用,P<0.05,联合用药组的q值分别为3.59和2.16,联合用药具有明显的G2/M期阻滞效应。蛋白质印记法结果显示,两药联合作用后,COX-2、bcl-2表达均低于单药组,bax和caspase-3表达均高于单药组。结论:AS2O3和COX-2抑制剂Celecoxib对上皮性卵巢癌细胞株单药有效,联合后具有显著的协同抗肿瘤效应。

Objective：To investigate the effects of the combination of Arsenic Trioxide and COX -2 inhibitor Celecoxib in ePithelial ovarian cancer cells and the mechanisms. Methods：In OVCAR-3 cells,the dose-dePendent anti-cancer effects were observed when AS2 O3 or Celecoxib was aPPlied as a single agent,and the combination effects of the two agents. APoPtosis and cell cycle status was tested by Flow Cytometry and Western blot were aPPlied. Results：Dose-dePendent anti-Proliferative effects on OVCAR-3 cells were observed when AS2 O3 or Celecoxib was aPPlied as single agent,the IC50 value was 4. 72μmol/L and 42. 58μmol/L resPectively. When the two agents were aPPlied simultaneously,the growth inhibition rate was higher significantly than that of the grouP treated with sin-gle-agent AS2O3 or Celecoxib（P〈0. 05）. The results of Flow Cytometry testing showed significant G2/M Phase block and increased aPoPtosis rate when the two agents were aPPlied simutaneously. COX-2 and bcl-2 exPression of the two-agent treatment grouP was down-regulated,bax and casPase-3 were uP-regulated comPared with single-agent AS2 O3 or Celecoxib treated grouP. Conclusion：There are synergistic effects when arsenic trioxide and Cele-coxib were used in combination in ePithelial ovarian cancer cell line.