中文摘要：

目的探讨活性氧（reactive oxygenspecies，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cleavedcaspase-3，Bcl-2的表达降低，Bax的表达增高，easpase-3抑制剂Ac-DEVD-CHO和caspase抑制剂z-VAD-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。

英文摘要：

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.