Objective: To investigate the anti-neoplastic effects of selective cyclooxygenase-2 inhibitor NS398 on proliferation and apoptosis of human breast cancer cell line MCF-7, and to preliminarily explore its molecular mechanism.Methods: MCF-7 cells were treated with NS398 at different concentrations for a period ranging from 24 to 72 hours.MTT assay was used to detect the proliferation of MCF-7 cells.Flow cytometry ( Annexin V-FITC/PI ) was performed to analyze the apoptosis of MCF-7 cells.The expression of COX-2 was measured by Western blot, and the levels of VEGF and PGE2 were measured by ELISA.Results: NS398 inhibited proliferation of the MCF-7 cells.The inhibitory effect varied with the different concentrations of NS398 and the exposure time.Across a single drug exposure time period, there were statistical differences among the 4 concentrations of NS398, i.e., 10 μmol/L, 20 μmol/L, 40 μmol/L and 80 μmol/L ( P ＜ 0.001 ).NS398 downregulated the expression of COX-2 protein in MCF-7 cells.Levels of VEGF and PGE2 were suppressed by NS398.There was a significant negative correlation between the apoptotic rate of MCF-7 cells and the levels of VEGF and PGE2.Conclusion: NS398 inhibits the proliferation of human breast cancer cell line MCF-7 and induces apoptosis.The mechanism may be associated with downregulation of COX-2 and inhibition of VEGF and PGE2.%目的:探讨选择性环氧化酶-2(cyclooxygenase-2,COX-2)抑制剂N-[2-(cyclohexyloxy)4-nitrophenyl]-methanesulfonamide(NS398)对人乳腺癌细胞系MCF-7增殖和凋亡的影响及其相关机制.方法:用不同浓度的选择性COX-2抑制剂NS398处理MCF-7细胞,采用四甲基偶氮唑蓝(MTT)法检测选择性COX-2抑制剂NS398对MCF-7细胞增殖的影响;流式细胞仪Annexin V-FITC/PI双染法检测人乳腺癌细胞系MCF-7的凋亡情况;Western-blot法测定NS398作用于MCF-7细胞后的COX-2蛋白表达水平;酶联免疫吸附试验(ELISA)检测NS398作用于MCF-7细胞后的细胞培养上清中血管内皮生长因子VEGF和前列腺素E2(PGE2)释放水平.结果:选择性COX-2抑制剂NS398能抑制人乳腺癌细胞系MCF-7细胞生长,NS398药物浓度不同,孵育时间不同时,其对人乳腺癌细胞MCF-7的增殖抑制效应不同.作用同一时间时,10、20、40、80 μmol/L 4个浓度之间差异有统计学意义(P<0.001);NS398作用于MCF-7细胞后能下调COX-2蛋白表达;NS398能明显抑制MCF-7细胞VEGF和PGE2的释放水平,且MCF-7细胞凋亡抑制率与VEGF和PGE2释放水平呈显著负相关.结论:选择性COX-2抑制剂NS398可抑制人乳腺癌细胞系MCF-7细胞增殖,其机制可能与选择性COX-2抑制剂NS398作用于MCF-7细胞后COX-2蛋白表达下调,VEGF和PGE2释放水平下降有关.
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