选择性COX-2抑制剂NS-398对宫颈癌细胞的作用及其作用机制

目的:研究选择性COX-2抑制剂NS-398对宫颈癌细胞的作用及其作用机制,探讨NS-398与卡铂在宫颈癌治疗中的协同作用.方法:用NS-398、卡铂及两者联合作用人宫颈癌Hela细胞,四甲基偶氮唑盐(MTT)比色法检测NS-398、卡铂及两者联合对宫颈癌细胞增殖的影响,流式细胞仪PI染色法分析NS-398、卡铂处理后宫颈癌细胞凋亡率和细胞周期的改变.结果:NS-398、卡铂对人宫颈癌hela细胞的增殖具有抑制作用.卡铂联合NS-398对人宫颈癌hela细胞的增殖抑制作用显著增加,其联合抑制率近似于NS-398和卡铂单药抑制率之和,也近似于2倍卡铂剂量时的增殖抑制率.流式细胞仪检测发现,与对照组比较,NS-398处理组G1期细胞明显增加,而S期细胞明显减少,两组比较差异有统计学意义(P＜0.05);而卡铂处理组G1期细胞明显减少,S期细胞明显增加,两组比较有统计学意义(P＜0.05).NS-398(200 μmol/L)作用Hela细胞48 h后,流式细胞仪检测发现,NS-398处理组凋亡率为3.43%±0.02%,对照组凋亡率为1.48%±0.03%,两组比较差异无统计学意义(P＞0.05).而卡铂(80 mg/L)处理组凋亡率为9.32%±0.02%,与对照组比较差异有统计学意义(P＜0.05).结论:选择性COX-2抑制剂NS-398对宫颈癌细胞的增殖具有抑制作用.NS-398对宫颈癌细胞的作用可能与凋亡无关.NS-398与卡铂在宫颈癌化疗中具有叠加作用.

Mechanism and effect of selective cyclooxygenase-2 inhibitorNS-398 on human cervical carcinoma cells

OBJECTIVE: To investigate the effect and mechanism of the selective COX-2 inhibitor NS-398 and carboplatin on the human cervical carcinoma cell line Hela. METHODS: The effect of NS-398, carboplatin, and both on the proliferation of Hela cells was assessed by methylthiazolete trazolium (MTT) method, and the apoptosis assay and cell cycle distribution were analyzed by flow cytometry. RESULTS: NS-398, and carboplatin inhibited the growth of Hela cells in a dose and time-dependent manner. When combining carboplatin with NS-398, the combined inhibition rate was increased, which nearly equaled the inhibition rate of the double concentrations of carboplatin. Flow cytometry demonstrated that the cell cycle was redistributed: the G(1)-phase cell fraction was increased while the S-phase cell fraction was significantly decreased after the cells were treated with NS-398 (P<0.05), However,the result was just the opposite after being treated with carboplatin. The apoptotic rate was 1.48%+/-0.03% and 3.43%+/-0.02% for pre-treatment and post-treatment with NS-398 respectively (P>0.05) while the apoptotic rate was 9.32%+/-0.02% after the treatment with carboplatin (P<0.05). CONCLUSION: NS-398 can inhibit the growth of Hela cells. The effect of NS-398 on Hela cells may not be related to the apoptosis. NS-398 and carboplatin can bring about synergistic effect in chemotherapy on Hela cells.