摘要
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.
出处
《现代肿瘤医学》
CAS
2015年第13期1805-1809,共5页
Journal of Modern Oncology