环氧化酶-2抑制剂nimesulide对乳腺癌细胞株增生、凋亡的影响

目的 探讨环氧化酶-2抑制剂nimesulide(NIM)对雌激素受体(ER)阴性(MDA-MB．231)和阳性(MCF-7)人乳腺癌细胞株增生、凋亡的影响。方法 应用MTT比色法分析细胞生长抑制作用，流式细胞技术测定细胞周期分布和凋亡率，透射电镜观察细胞形态与超微结构，AnnexinV法检测细胞的凋亡。结果 NIM以时间、剂量依赖性方式抑制MDA-MB-231(COX-2阳性)、MCF-7(COX-2阴性)细胞生长，阻滞细胞周期于G0／G1期，诱导细胞的凋亡，MDA—MB-231细胞对NIM的作用更为敏感。NIM对COX-2表达阴性的MCF-7细胞同样具有抑制增生、诱导凋亡的作用。结论 NIM对ER阳性和ER阴性乳腺癌细胞均有抑制增生、诱导凋亡的作用。NIM的抗肿瘤作用存在环氧化酶．2依赖性与非依赖性两种途径。

The effect of cyclooxgenase-2 inhibitor nimesulide on proliferation and apoptosis of breast cancer cell lines

Objective To investigate the effect of nimesulide(NIM) on human breast cancer cell lines, including MDA?- MB?- 231(estrogen receptor?- negative) and MCF?- 7 (estrogen receptor?- positive). Methods MDA?- MB?- 231 and MCF?- 7 human breast carcinoma cell lines were treated with NIM in vitro. Cell proliferation was evaluated by MTT assay, distribution of cell cycle and rate of apoptosis were determined by flow cytometry, meanwhile the rates of apoptosis were estimated on the basis of Annexin V apoptosis detection. The apoptosis was confirmed by ultrastructural alternations. Results The inhibitory effects of NIM on proliferation of MDA?- MB?- 231 and MCF?- 7 cells were associated with cell cycle arrest in G0/G1 phase and with induction of apoptosis, in a time and dose?- dependent manner. Simultaneously, NIM may also inhibit proliferation and stimulate apoptosis of MCF?- 7 cells. Conclusions NIM inhibits proliferation and induces apoptosis not only in ER?- positive, but also in ER?- negative breast cancer cells. There were two different mechanisms underlying the anti?- carcinogenic action of NIM, namely, dependent on the expression of COX?- 2 protein or not.