选择性COX-2抑制剂塞来昔布对乳腺癌的放疗增敏作用及其机制研究  

Radiosensitization of Selective Cyclooxygenase-2 Inhibitor,Celecoxib in Breast Cancer and its Mechanism

作　　者：牛国梁[1] 王辉[1] 谢荣俊[1] 张树友[1] 

机构地区：[1]南华大学附属南华医院,湖南衡阳421002

出　　处：《肿瘤学杂志》2011年第3期172-176,共5页Journal of Chinese Oncology

基　　金：湖南省科技厅基金资助(2008FJ3086)

摘　　要：[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。[Purpose] To investgate radiosensitization of selective cyclooxygenase-2 inhibitor,Celecoxib in breast cancer and its mechanism.[Methods] The MDA-MB-231 cell line in logarithmic phase was divided into four groups： control group,drug group,radiation group and experimental group（radiation ＋Celecoxib）.The change of cell cycle and apoptosis rate was analyzed by flow cytometry（FCM）.The radiotherapy sensitization effect was detected by clone formation experiment.COX-2,Bcl-2 and VEGF expression were detected by Western blot method.[Results] The different concentrations of Celecoxib could obviously inhibit MDA-MB-231 cell growth and in a dose dependent manner.FCM result showed that with concentrations of Celecoxib increasing,the cell cycle was significantly changed（G0/G1 phase ratio increased and S phase ratio decreased）.The apoptosis rate of experimental group was significantly higher than that in radiation group（31.20%±1.27% vs 17.99%±1.01%,t=2.43,P=0.025）.Compared with radiation group,the radiosensitization values of Dq,Do and SF2 in experimental group were significantly decreased.Celecoxib inhibited expression of COX-2,VEGF and Bcl-2（P0.05）.[Conclusion] The selective cyclooxygenase-2 inhibitor,Celecoxib can obviously inhibit human breast cancer MDA-MB-231 cell growth.The possible mechanism is inhibit COX-2 expression,induce apoptosis of tumor cell,adjust the cell cycle and inhibit angiogenic factors.

关 键 词：COX-2抑制剂 塞来昔布 乳腺肿瘤 放疗增敏作用 

分 类 号：R737.9[医药卫生—肿瘤]