Induction of G0/G1 cell cycle arrest in ovarian carcinoma cells by the anti-inflammatory drug NS-398, but not by COX-2-specific RNA interference.

摘要: Cyclooxygenases, particularly COX-2, play an important role in tumor development and progression. We have previously shown that COX-2 expression is independent prognostic factor human ovarian carcinoma. In this study, we investigated the effects of inhibition COX isoforms by NSAID NS-398 as well COX-isoform-specific RNA interference (RNAi) carcinoma cell lines OVCAR-3 SKOV-3. cells showed a constitutive COX-1 induction high levels PGE(2) after stimulation with interleukin-1beta. contrast, SKOV-3 were negative for both isoforms. cells, production was inhibited concentrations 1 microM COX-2-specific silencing (siRNA), while COX-1-specific siRNA did not effect. This suggests major source line. To dissociate non-COX-2-specific on proliferation, proliferation assay performed incubation siRNAs. induced at 50-500 microM, which are above needed production. inhibitory effect present COX-positive line COX-negative could be reverted addition exogenous PGE(2). Neither COX-1- nor siRNAs had cells. Cell cycle analysis increased accumulation G0/G1 phase treatment NS-398, but These experiments suggest reduced arrest inhibition. Our study shows specific RNAi used to NSAIDs. Furthermore, our results one primary mechanisms responsible antiproliferative