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目的 :探讨选择性环氧合酶 2 (COX- 2 )抑制剂NS -398与前列腺素E(PGE2 )对子宫内膜异位症患者子宫内膜细胞COX -2mRNA表达与细胞凋亡的影响。方法 :以体外培养的子宫内膜细胞为研究对象 ,分别用NS- 398与PGE2 处理。采用RT- PCR法、MTT法、酶联免疫吸附试验 (ELISA)和流式细胞术 ,检测刺激前后COX -2mRNA表达量、细胞增殖、凋亡与细胞周期分布情况以及上清液中凋亡抑制蛋白Bcl 2与PGE2 的释放量。结果 :NS- 398以剂量与时间依赖方式抑制COX -2mRNA的表达以及PGE2 与Bcl -2的分泌 ,抑制子宫内膜细胞增殖 ,诱导细胞凋亡 ,改变细胞周期分布 ,增加G0 /G1期细胞的比例。PGE2以时间与剂量依赖方式刺激子宫内膜细胞的COX- 2mRNA的表达 ,使Bcl- 2释放增加。同时 ,PGE2 可以逆转NS- 398对子宫内膜细胞的抑制作用 ,细胞增殖重新活跃 ,改变细胞周期分布 ,减少G0 /G1期细胞的比例 ,抑制细胞凋亡。结论 :COX- 2选择性抑制剂NS- 398,促进细胞凋亡 ,抑制细胞增殖 ,其机制可能与抑制COX -2的表达 ,降低PGE2 以及Bcl- 2释放 ,和改变细胞周期有关。PGE2 在体外能够刺激子宫内膜细胞COX- 2的表达升高 ,促进细胞增殖 ,抑制细胞凋亡。
Objective: To investigate the effect of selective cyclooxygenase 2 (COX-2) inhibitor NS-398 and prostaglandin E (PGE2) on the expression of COX-2 mRNA and apoptosis of endometrial cells in patients with endometriosis. Methods: Endometrial cells were cultured in vitro and treated with NS-398 and PGE2 respectively. The expression of COX-2 mRNA, cell proliferation, apoptosis and cell cycle distribution and the inhibition of apoptosis in supernatant were detected by RT-PCR, MTT, ELISA and flow cytometry The release of protein Bcl 2 and PGE2. Results: NS-398 inhibited the expression of COX-2 mRNA and the secretion of PGE2 and Bcl-2 in a dose and time-dependent manner, inhibited the proliferation of endometrial cells, induced apoptosis, altered the cell cycle distribution and increased the expression of COX- proportion. PGE2 stimulated the expression of COX-2 mRNA in endometrial cells in a time-and dose-dependent manner, and increased the release of Bcl-2. At the same time, PGE2 can reverse the inhibitory effect of NS-398 on endometrial cells, and the cell proliferation reactivated, changing the cell cycle distribution, decreasing the proportion of G0 / G1 phase cells and inhibiting the apoptosis. CONCLUSION: NS-398, a selective inhibitor of COX-2, can promote cell apoptosis and inhibit cell proliferation. Its mechanism may be related to inhibiting the expression of COX-2, decreasing the release of PGE2 and Bcl-2, and changing the cell cycle. PGE2 can stimulate the expression of COX-2 in endometrial cells in vitro, promote cell proliferation and inhibit apoptosis.