Inhibitory effects of a cyclooxygenase-2 inhibitor,NS398,on cancer cells

AIM: To study the mechanism of growth inhibitory effect of a selective cyclooxygenase-2(COX-2) inhibitor,NS-398,on cancer cells.METHODS: The esophageal cancer cell line(EC9706),which expresses COX-2 constitutively,and hepatocellular carcinoma cell line(SMMC7721),which expresses no COX-2,were studied.The cell lines were incubated with NS-398 at doses of 10,20,50,100 μmol/L for 24 h,48 h and 72 h.Antiproliferation effect was measured by -TdR incorporation.The cell apoptosis were determined by flow cytometry(FCM) and DNA fragmentation analysis.Survivin was detected by immunocytochemical technique.RESULTS: The growth inhibition was induced by NS398 in a dose-and time-dependent manners in both cell lines.FCM analysis revealed a high sub-G_1 cell peak in EC9706 group and agarose electrophoresis showed marked apoptosis ladder pattern.However,no apoptosis was observed in SMMC7721 cells treated with NS-398.The difference of apoptosis percentage in EC9706 and SMMC7721 was(45.23±1.08)% and(3.05±0.15)%(P0.01).After 24 h incubation with NS398 at concentration of 100 μmol/L,the expression of survivin was markedly reduced in EC9706,no change was observed in SMMC7721.CONCLUSION: NS-398 suppresses cell growth in cancer cell lines by different mechanism.NS-398 suppresses cell growth and increases apoptosis in the cancer cells that expresses COX-2.