The study of selective cyclooxygenase-2 inhibitor NS-398 on proliferation and apoptosis of human colon cancer cells

Objective To investigate the influence of NS-398, a selective cyclooxygenase(COX)-2 inhibitor, on the proliferation and apoptosis of colorectal cancer cell HT-29, and to explore its potential mechanism. Methods Cultured HT-29 cells were treated with NS-398. MTT assay and flow cytometry were used to measure the proliferation and apoptosis. RT-PCR analysis was performed to measure the level of COX-2 mRNA expression at different time points in HT-29 cells. The expression of prostaglandin (PG)E2,Cyclin D1 and Bcl-2 were measured by ELISA and Western blot, respectively.Results High expression of COX-2 mRNA was detected in colorectal cancer cell line HT-29 and no obvious change of COX-2 mRNA was found after the treatment of NS-398 . NS-398 inhibited the cells proliferation and induced apoptosis in a dose-and time-dependent manner, and resulted in a significant down-regulation of Cyclin D1, Bcl-2 and PGE2.Conclusions Our results show that NS-398 may inhibit the proliferation and induce apoptosis of colon cancer cell lines HT-29 through decreasing expression of Cyclin D1 and Bcl-2 . COX-2 activity rather than its mRNA expression was related to NS-398-mediated pathway on HT-29 cells. This may be a new interfering target of selective COX-2 inhibitor on colon cancer.