Abstract: AIM: To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibitor, NS398, on cell cycle and related cyclin-dependent kinase inhibitors p21^waf1/cip1 and p27^kip1/pic2 in human pancreatic carcinoma cells. METHODS: SW1990 human pancreatic carcinoma cells were treated with NS398 (100 μmol/L), prostaglandin E2 (PGE2, 10 nmol/L) and their combination, respectively.The inhibitory effects of NS398 on SW1990 cell were detected by using MTT assay.The cell cycle was measured with flow cytometry.The level of intracellular PGE2 was determined with ELISA.The mRNA of p21^waf1/cip1and p27^kip1/pic2was detected by semi-quantitative RT-PCR.The expression of p21^waf1/cip1 and p27^kip1/pic2 protein was detected by Western blotting analysis. RESULTS: NS398 inhibited the growth of SW1990 cell and decreased level of intracellular PGE2 in a dose-dependent manner.NS398 caused cell accumulation in G0 G1 phase that was 11 % higher than control.The mRNA and protein of p21^waf1/cip1and p27^kip1/pic2were up-regulated by NS398.PGE2 stimulated cell growth, but factorial experiment showed that 10 nmol/L of PGE2 could not antagonize inhibitory effects of cell growth, cell cycle distribution, transcription and expression of COX-2, p21^waf1/cip1 and p27^kip1/pic2 induced by NS398 in SW1990 cells. CONCLUSION: The results suggest that selective COX-2 inhibitor, NS398, can induce inhibitory effects of cell growth and G0 G1 cell cycle arrest in SW1990 cells by upregulation of p21^waf1/cip1 and p27^kip1/pic2 and may be not dependent of PGE2 pathway.

Key words: pancreatic neoplasms, NS398, cyclooxygenase, prostaglandin E₂, cell cycle