氧化应激参与戊地昔布诱导的人乳腺癌MCF-7/ADR细胞凋亡

Oxidative Stress is Involved in the Apoptosis of Human Breast Cancer MCF-7 / ADR Cells Induced by Valdecoxib

目的探讨氧化应激在选择性环氧化酶-2抑制剂戊地昔布诱导人乳腺癌MCF-7/ADR细胞凋亡中的作用。方法用噻唑蓝法检测药物对人乳腺癌MCF-7/ADR细胞生长的作用;用流式细胞仪和Hoechst 33258染色检测人乳腺癌MCF-7/ADR细胞凋亡;用试剂盒检测还原型谷胱甘肽和氧化型谷胱甘肽的含量;用激光共聚焦检测细胞内活性氧水平。结果 1戊地昔布可诱导人乳腺癌MCF-7/ADR细胞凋亡,抑制细胞生长。2Caspase 3抑制剂Ac-DEVD-CHO和Caspase抑制剂Z-VAD-FMK可拮抗戊地昔布的作用。3戊地昔布可降低细胞还原型谷胱甘肽/氧化型谷胱甘肽比值,提高MCF-7/ADR细胞内的活性氧水平,抗氧化剂N-乙酰半胱氨酸可拮抗戊地昔布的抗肿瘤作用。结论戊地昔布可诱导人乳腺癌MCF-7/ADR细胞凋亡,与其升高细胞内的活性氧有关。

OBJECTIVE To study the effect of selective COX（ cyclooxygenase）-2 inhibitor valdecoxib on the growth of human breast cancer MCF-7 / ADR（ MCF-7 / adriamycin） cells. METHODS MTT assay was used to observe the effect of drugs on the growth of cells. Flow cytometry and Hoechst 33258 dye were used to detect apoptosis of MCF-7 / ADR cells. The levels of GSH and GSSG were detected by kit; Laser confocal microscopy was used to detect the levels of ROS. RESULTS Valdecoxib significantly inhibited the growth of human breast cancer MCF-7 / ADR cells and induced apoptosis of the cells. Caspase 3 inhibitor Ac-DEVD-CHO and caspase inhibitor Z-VAD-FMK antagonized the inhibitory effect of valdecoxib on MCF-7 / ADR cell growth. Valdecoxib significantly decreased GSH / GSSG ratio and increased the level of ROS,and antioxidant N-acetylcysteine antagonized the inhibitory effect of valdecoxib on MCF-7 / ADR cell growth. CONCLUSION The apoptosis of human breast cancer MCF-7 / ADR cells induced by valdecoxib is associated with increase of ROS.