戊地昔布通过上调ROS诱导人乳腺癌MCF-7细胞凋亡  

Valdecoxib induces apoptosis of human breast cancer MCF-7 cells by increasing ROS

作　　者：张曼丽[1,2] 王慧慈[1] 柳金金[1] 于丁[3] 王紫微[4] 吴佳昕[4] 李军霞[1] 

机构地区：[1]河北医科大学药理教研室,河北石家庄050000 [2]沧州市人民医院甲乳外科,河北沧州061000 [3]河北医科大学第二医院心外科,河北石家庄050000 [4]河北医科大学

出　　处：《基础医学与临床》2015年第4期491-495,共5页Basic and Clinical Medicine

基　　金：河北省科技攻关项目(07276403D);河北省卫生厅医学重点课题(2008067)

摘　　要：目的探讨活性氧(reactive oxygen species,ROS)在选择性环氧化酶(cyclooxygenase,COX)-2抑制剂戊地昔布诱导人乳腺癌MCF-7细胞凋亡中的作用。方法噻唑蓝(MTT)法检测细胞增殖;流式细胞术和Hoechst33258检测细胞凋亡;激光共聚焦显微镜观察细胞ROS和线粒体膜电位;Western blot检测蛋白表达。结果 1)戊地昔布可诱导细胞凋亡(P<0.01),抑制细胞增殖(P<0.05或P<0.01)。2)给予戊地昔布后,caspase-3表达先升高,然后降解为cleaved caspase-3,Bcl-2的表达降低,Bax的表达增高,caspase-3抑制剂Ac-DEVD-CHO和caspase抑制剂ZVAD-FMK可拮抗戊地昔布的抗肿瘤作用(P<0.05或P<0.01)。3)戊地昔布可降低线粒体膜电位,明显提高细胞内的ROS水平。抗氧化剂N-乙酰基半胱氨酸(N-Acetyl-L-cystein,NAC)可拮抗戊地昔布的抗肿瘤作用(P<0.01)。结论戊地昔布可通过升高细胞内ROS诱导MCF-7细胞凋亡。Objective To study the role of ROS in the apoptosis of human breast cancer MCF-7 cells induced by valdecoxib, a selective COX-2 inhibitor. Methods MTI assay was used to observe the effect of valdecoxib on cell proliferation; Flow cytometry and hoechst 53258 dye were used to detect apoptosis; Laser confocal microscopy was used to detect the level of ROS and mitochondrial transmembrane potential; Western blot was used to detect the pro- tein expression. Results 1 ） Valdecoxib significantly inhibited the proliferation of MCF-7 cells （P 〈 0. 05 or 0. 01 ） and induced apoptosis of the cells（P 〈0. 01 ）. 2）The expression of Bax was increased, and the expression of Bcl-2 was decreased after valdecoxib was aplied. The expression of caspase-3 was increased at first and then degradated into cleaved caspase-3. Caspase-3 inhibitor Ac-DEVD-CHO, and caspase inhibitor Z-VAD-FMK antagonized the growth inhibition effect of valdecoxib （P 〈 0. 05 or 0. 01 ）. 3 ） Valdecoxib significantly decreased the mitochondrial trans- membrane potential, and increased the level of ROS. Antioxidant NAC antagonized the growth inhibition effect ofvaldecoxib （P 〈 0. 01 ）. Conclusions Valdecoxib induces apoptosis of MCF-7 cells by enhancing the level of ROS.

关 键 词：戊地昔布 环氧化酶-2 人乳腺癌MCF-7细胞 凋亡 活性氧 

分 类 号：R737.9[医药卫生—肿瘤]