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[目的]探讨选择性环氧化酶-2(COX-2)抑制剂塞来昔布对人乳腺癌细胞的放疗增敏作用及其可能的机制。[方法]取对数生长期MDA-MB-231细胞株,实验分为对照组、药物组、照射组及实验组(照射线+塞来昔布)。流式细胞术(FCM)检测细胞周期变化和各组凋亡率;克隆形成实验检测放射增敏作用;Western blot法检测COX-2、VEGF、Bcl-2蛋白表达。[结果]不同浓度塞来昔布对MDA-MB-231细胞有明显抑制作用,且呈剂量依赖性(F=5.56,P=0.030)。FCM检测结果显示,随塞来昔布浓度增加,细胞周期明显变化(G0/G1期比例增高,S期比例降低)。实验组凋亡率较照射组明显高(31.20%±1.27%vs 17.99%±1.01%,t=2.43,P=0.025)。克隆形成实验显示,实验组与照射组相比较,反映放射敏感性指标的Dq、Do和SF2显著降低。塞来昔布能抑制COX-2、VEGF和Bcl-2蛋白表达(P<0.05)。[结论]选择性COX-2抑制剂塞来昔布对人乳腺癌MDA-MB-231细胞有明显的放射增敏作用,其可能的机制是抑制COX-2表达、诱导细胞凋亡、调节细胞周期分布和抑制细胞血管生成因子生成。
[Objective] To investigate the radiosensitizing effect of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on human breast cancer cells and its possible mechanism. [Method] The MDA-MB-231 cell line in logarithmic growth phase was taken. The experiment was divided into control group, drug group, irradiation group and experimental group (irradiation + celecoxib). Flow cytometry (FCM) was used to detect cell cycle changes and apoptotic rates in each group. Clonal formation assay was used to detect the radiosensitivity. Western blot was used to detect the protein expression of COX-2, VEGF and Bcl-2. [Results] Celecoxib at different concentrations had a significant inhibitory effect on MDA-MB-231 cells in a dose-dependent manner (F = 5.56, P = 0.030). The result of FCM showed that with the increase of celecoxib concentration, the cell cycle changed significantly (the proportion of G0 / G1 phase increased and the proportion of S phase decreased). The apoptosis rate in the experimental group was significantly higher than that in the irradiated group (31.20% ± 1.27% vs 17.99% ± 1.01%, t = 2.43, P = 0.025). Clone formation experiments showed that compared with the irradiated group, Dq, Do and SF2, which reflect the radiosensitivity index, were significantly decreased. Celecoxib inhibited COX-2, VEGF and Bcl-2 protein expression (P <0.05). [Conclusion] Celecoxib, a selective COX-2 inhibitor, has a significant radiosensitizing effect on human breast cancer MDA-MB-231 cells. The possible mechanism is that it inhibits the expression of COX-2, induces apoptosis, regulates cells Cyclic distribution and inhibition of angiogenic factor production.