塞来昔布对乳腺癌细胞株的放射增敏作用

Effect of celecoxib on radiosensitization of breast cell lines

背景与目的:塞来昔布(celecoxib)能有效增强放射线对肿瘤的作用,但其作用机制尚不清楚。本研究探讨塞来昔布对人乳腺癌MDA-MB-231细胞放射增敏的作用机制。方法:取对数生长期MDA-MB-231细胞株2×106个,分为对照组、药物组、照射组及实验组(照射线联合塞来昔布),流式细胞分析法(flow cytometry,FCM)检测各组细胞凋亡率;克隆形成实验检测放射增敏作用;Western blot法检测Akt、pAkt蛋白表达。结果:实验组凋亡率[(31.20±1.27)%]显著高于照射组[(17.99±1.01)%](t=14.01,P<0.05);与照射组相比较,实验组反映放射敏感性的指标准域剂量(Dq)、平均致死剂量(DO)、2 Gy照射的存活分数(SF2)值均显著降低(0.437 vs 1.175,1.874 vs 2.394,0.52 vs 0.79),放射增敏比(SERD0)为1.277;各组Akt蛋白表达无明显差异,但塞来昔布能抑制pAkt的表达,而放射线能上调其表达,两者联合使用对pAkt表达有明显抑制作用(P<0.05)。结论:塞来昔布对人乳腺癌MDA-MB-231细胞有放射增敏作用,其可能的机制是阻断PI3K/Akt信号通路的活化,从而提高乳腺癌放射敏感性。

Background and purpose:Celecoxib has been reported to sensitize tumor cells to irradiation,but the mechanism of the radiosensitization is still unclear.The purpose of this experiment was to investigate the effect of celecoxib on the radiosensitivity of human breast cancer cells.Methods:The MDA-MB-231 cell line in the logarithmic phase was divided into 4 groups:the control group,drug group,radiation group and the case group(radiation+celecoxib).The apoptosis rate was analyzed using flow cytometry(FCM).The radiosensitization effect was detected using clone formation experiment.Akt and pAkt protein expressions were detected by Western blot method.Results:Apoptosis rate in the case group was significantly higher than that of the radiation group,at(31.20±1.27)% and(17.99±1.01)%,respectively(P<0.05).The values of Dq,D0 and SF2 in the case group significantly decreased compared with those in the radiation group.SERD0 was at 1.277 according to the clonogenic assay.Celecoxib inhibited pAkt expression,whereas radiation increased pAkt expression,but both celecoxib and radiation in the case group significantly inhibited pAkt expression.Conclusion:Celecoxib obviously has a radiotherapy sensitization effect on human breast cancer MDA-MB-231 cell,and the downregulation of the PI3K/Akt signaling pathway may involve in the radiosensitization.