Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis

OLIVARES C; BILOTAS M; BUQUET RA; BORGHI M; SUELDO C; TESONE M; MERESMAN GF

HUMAN REPRODUCTION

Año: 2008 vol. 23 p. 2701 - 2708

0268-1161

BACKGROUND Celecoxib, a selective COX-2 inhibitor, also has both anti-proliferative properties and pro-apoptotic effects on different in-vivo and in-vitro models, two actions that have been suggested to be efficacious in therapy for endometriosis. We evaluated the effects of this agent on apoptotic and proliferative response, VEGF production and COX-2 expression and activity of endometrial epithelial cells (EEC) from patients with endometriosis. METHODS and RESULTS: 32 endometriosis and 13 control women were included in the study. EEC from eutopic endometrium biopsies were cultured with different doses of celecoxib. Celecoxib at 50 µM, 75 µM and 100 µM inhibited EEC proliferation in cultures from controls (p<0.05) and patients with endometriosis (p<0.05) as assessed by 3H-thymidine uptake. Celecoxib at 50 µM, 75 µM and 100 µM induced apoptosis in EEC from controls (p<0.05) and patients with endometriosis (p<0.01) as revealed by the acridine orange-ethidium bromide technique. Western blot analysis showed that celecoxib was effective at inducing COX-2 expression at 100 µM (p<0.05). Celecoxib at 25, 50 and 100 µM was also effective in reducing COX-2 activity reflected in the reduction of PGE2 synthesis (p<0.01), and VEGF secretion (p<0.05), assessed by ELISA. CONCLUSIONS: This study suggests a direct effect of celecoxib on the reduction of endometrial growth and supports further research on selective COX-2 inhibition as a novel therapeutic modality in endometriosis.