Abstract

Cyclooxygenase-2 (COX-2) specific inhibitors block cell growth and induce apoptosis and cell arrest in various tumour cell lines. Also, it has been shown that COX-2 inhibitors, such as celecoxib, are potent inhibitors of angiogenesis, both in-vitro and in-vivo. We have previously shown that celecoxib inhibits proliferation and induces apoptosis in cultured endometrial epithelial cells (EEC) from patients with endometriosis (EDT) and controls. In the present study we evaluated the effect of celecoxib on in-vitro vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) secretion, as well as on COX-2 expression in EEC from EDT patients. Experimental in vitro study. Endometrial biopsies were taken during the proliferative phase in 13 untreated patients with EDT diagnosed by laparoscopy. Purification and culture of EEC were done according to the technique described by Meresman et al. (Fertil Steril, 2003). Cultures were treated with celecoxib in doses between 25 and 100 mM. COX-2 expression was assesed by western blot and immunocytochemistry. VEGF and PGE2 secretion were evaluated by ELISA. Statistical analysis was done by Kruskal-Wallis nonparametric ANOVA test, and Dunn´s multiple comparisons test. COX-2 expression was shown by immunocytochemistry in all celecoxib treated EEC cultures and in basal conditions. Western blot analysis for COX-2 showed no statistical change in protein expression in 25–75 mM celecoxib treated EEC. However, at 100 mM there was a significant increase in COX-2 expression (P<0.05). To determine whether COX-2 activity was affected by celecoxib treatment, PGE2 production was measured in conditioned medium from EEC after celecoxib treatment (25, 50 and 100 mM). All doses of celecoxib significantly inhibited COX-2 activity (P<0.001 vs. basal). We also evaluated the levels of VEGF in EEC treated with celecoxib or vehicle (basal). Celecoxib treatment significantly reduced VEGF levels in EEC from patients with EDT (25 mM, P<0.001; 50 mM, P<0.05 and 100 mM, P<0.001 vs. basal). Our data suggest that removal of negative feedback by celecoxib treatment results in COX-2 induction in EEC from patients with EDT. We also showed that treatment with celecoxib reduced VEGF levels as well as PGE2 production. These findings support the investigation of COX-2 inhibitors as a treatment option in EDT.

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