Effect of NS-398, a cyclooxygenase-2 selective inhibitor, on the cytotoxicity of cytotoxic T lymphocytes to ovarian carcinoma cells.

Cyclooxygenase-2 (COX-2) is a key limited enzyme of prostaglandin (PG) synthesis and has been demonstrated to be overexpressed in cancer. N-[2-(cyclohexyloxy)-4-nitropheny]-methane sulfonamide (NS-398) is a special inhibitor of COX-2 and may suppress PGE2 release and promote immune response mechanism of cytotoxic T lymphocytes (CTLs). We aimed to investigate the effect of NS-398 on the PGE2 release, proliferation of ovarian carcinoma cell line CAOV3, and immune cytotoxicity of CTLs. CAOV3 cells were incubated with 0, 50, and 100 μmol/L NS-398 for 24, 48, and 72 h. Cell viability was determined by trypan blue staining. PGE2 was measured using radioimmunoassay. CTLs were generated from peripheral blood mononuclear cells after stimulated by CAOV3 cells or CAOV3 cells treated with NS-398 when IL-2 existed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the cytotoxicity of CTLs. As expected, the amount, cell density, cellular volume, and growth speed of CAOV3 cells incubated with NS-398 were significantly decreased compared with control group. This difference became more obvious with an increase in the NS-398 concentration and incubation time. Similarly, PGE2 released from CAOV3 cells treated with 50 and 100 μmol/L NS-398 was significantly decreased compared with control group (P<0.05). There was also significance in PGE2 between the two groups treated with 50 and 100 μmol/L NS-398 (P<0.05). Compared with control group, the killing rates of CTLs to CAOV3 treated with 50 and 100 μmol/L NS-398 were significantly increased (P<0.05). However, there is no significant difference between them. Together, our results suggest that NS-398 could be useful in prevention and therapy of ovarian carcinoma.