Expression Of Cyclooxygenases In Ovarian Cancer Cell Lines And Effects Of Selective COX Inhibitors On Cell Growth

BACKGROUD AND OBJECTIVES:Ovarian cancer is the leading cause of death in gynecological cancers largely because distant metastasis has already occurred at time of diagnosis. More than 80% of human ovarian cancers are epithelial ovarian cancers (EOCs). The etiology is not fully understood, but an inflammatory process is involved. Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of arachidonic acid to prostaglandins H2 (PGH2). PGs are important mediators of inflammation. COX-1 provides cytoprotective effects, whereas COX-2 is both inducible and the major isoform of inflammatory cells. The role for COX-2 in many cancers has been confirmed, but the role of COX-1 remains unclear. As to the expression of COX isoforms in ovarian cancers as most reports focused on COX-2 rather than COX-1. COX-1 is a constitutive enzyme, whereas COX-2 is highly inducible by diverse stimuli including cytokines, growth factors, mitogens, and tumor promoters, and regulates inflammation, differentiation, mitogenesis, and angiogenesis. Recent clinical trials have indicated that long term use of aspirin will decrease the incidence of certain malignancies, including colorectal, oesophageal, breast, lung, and bladder cancers. Regular use of NSAIDs over 10 to 15 years reduces the relative risk of developing colorectal cancer by 40–50%.In this study, human OSE cell lines were used to examine the expression of COX isoforms and the effects of selective COX inhibitors on cells growth in vitro.METHODS:1. The expression of COX isoforms in human ovarian cancer cell lines SKOV-3 and OVCAR-3 was analyzed by Western blot.2. The effects of selective COX-1 inhibitor SC-560 and selective COX-2 inhibitor NS-398 on OSE cells growth in vitro were determined by MTT assays. Growth inhibitions of the cells were measured by MTT assay.3. The influences of SC-560 and NS-398 on cells cycle were analyzed by flow cytometry(FCM).4. PGE2 concentration before and after using SC-560 or NS-398 was determined by enzyme immunoassay kit.RESULTS:1. COX-1 expressed in SKOV-3 and OVCAR-3 cell lines, but COX-2 only expressed in OVCAR-3 cells. 2. SC-560 and NS-398 inhibited the growth of cells, but SC-560 has more effect on cells growth than NS-398 at the same dose and the same treated time. 3. SC-560 and NS-398 had little effect on cell cycle. But SC-560 could increase the rate of apoptosis, whereas NS-398 had little show such an effect.4. SC-560 and NS-398 effectively blocked PGE2 production.CONCLUSION:1. COX-1 expressed in SKOV-3 and OVCAR-3 cell lines, but COX-2 only expressed in OVCAR-3 cells.2. SC-560 and NS-398 inhibited the growth of cells, but SC-560 has more effect on cells growth than NS-398 at the same dose and the same treated time. SC-560 and NS-398 had little effect on cell cycle, but could increase the rate of apoptosis.3. SC-560 and NS-398 effectively blocked PGE2 production.The cyclooxygenase, COX-1 and COX-2, play an important role in ovarian cancec cancers. The selective cox-1 and cox-2 inhibitors may have potential for use in prevention and treatment of EOC in humans.