基础医学与临床 ›› 2015, Vol. 35 ›› Issue (4): 491-495.

• 研究论文 • 上一篇    下一篇

戊地昔布通过上调ROS诱导人乳腺癌MCF-7细胞凋亡

张曼丽1,王慧慈2,柳金金2,于丁3,王紫微1,吴佳昕1,李军霞1   

  1. 1. 河北医科大学
    2. 河北医科大学药理教研室
    3. 河北医科大学第二医院心外科
  • 收稿日期:2014-09-22 修回日期:2015-01-03 出版日期:2015-04-05 发布日期:2015-04-08
  • 通讯作者: 李军霞 E-mail:lyjunxia@aliyun.com
  • 基金资助:
    多靶点抗肿瘤制剂研究;戊地昔布联合顺铂抗Lewis肺癌作用

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

  • Received:2014-09-22 Revised:2015-01-03 Online:2015-04-05 Published:2015-04-08

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Z-VAD-FMK可拮抗戊地昔布的抗肿瘤作用(P<0.05或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。

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

Abstract: 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 MTT assay was used to observe the effect of valdecoxib on cell proliferation; Flow cytometry and hoechst 33258 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 protein 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 apllied. The expression of caspase-3 was increased at first and then degradated to 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 transmembrane potential, and increased the level of ROS. Antioxidant NAC antagonized the growth inhibition effect of valdecoxib(P< 0.01). Conclusion valdecoxib induces apoptosis of MCF-7 cells by increasing the level of ROS.

Key words: valdecoxib, cyclooxygenase-2, human breast cancer cell line MCF-7, apoptosis, ROS