Effects of a selective cyclooxygenase-2 inhibitor, nimesulide, on the growth of ovarian carcinoma in vivo

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Abstract

New therapies against cancer are based on targeting cyclooxygenase-2 (COX-2). Whether COX-2 inhibitor therapy would be beneficial in the prevention and/or treatment of ovarian cancer still remains unclear. This study was designed to investigate whether nimesulide, a COX-2 selective inhibitor, could suppress tumor growth in implanted ovarian carcinoma mice and to explore the molecular mechanisms. Human ovarian SKOV-3 carcinoma cells xenograft-bearing mice were treated with nimesulide 62.5 mg/kg or 250 mg/kg alone i.g., daily for 21 days. Microvessel density (MVD) of ovarian carcinoma was determined with anti-CD34 as the label. Prostaglandin E2 (PGE2) levels were also determined by ELISA. In addition, the expression of COX-2 and COX-1 at protein and mRNA levels in the control groups was also detected by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). Nimesulide treatment showed a dose-dependent growth-inhibitory effect of human ovarian SKOV-3 tumors. The inhibitory rates in nimesulide 62.5 mg/kg group and 250 mg/kg group were 20.40% and 50.55% respectively, however, which is not significant statistically compared with that of control group (P > 0.05). In treatment groups, nimesulide significantly reduced intratumor PGE2 levels (all, P < 0.01). Microvessel densities in treatment groups were 61.20 ± 1.67 (62.5 mg/kg) and 66.27 ± 1.20 (250 mg/kg), which are significant statistically compared with that of control group (79.97 ± 1.07) (all, P < 0.01). However, COX-1, not COX-2, mRNA, and protein levels are elevated in tumor tissues. Nimesulide decreased microvessel density is associated with the reduction of PGE2 levels but without affecting growth inhibition and the expression of COX-2. Importantly, tumor growth implanted in SKOV-3 mice was not significantly attenuated suggesting that COX-1 in ovarian carcinoma tissue also has an important role in tumor growth. These findings may implicate COX-1 as a suitable target for the treatment of ovarian cancer.

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