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

BACKGROUND: Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, also has anti-proliferative properties and pro-apoptotic effects on different in vivo and in vitro models, two actions that may be efficacious in therapy for endo-metriosis. We evaluated the effects of celecoxib on apoptosis and proliferation, and vascular endothelial growth factor (VEGF) production and COX-2 expression and activity in endometrial epithelial cells (EECs). METHODS AND RESULTS: Thirty-two endometriosis and 13 control women were included in the study. EECs from eutopic endome-trium and control biopsies were cultured with different doses of celecoxib. Celecoxib at 50, 75 and 100 mM (versus vehicle control) inhibited EEC proliferation in cultures from controls (P < 0.05, P < 0.01 and P < 0.01, respectively) and patients with endometriosis (P < 0.05, P < 0.01 and P < 0.01), as assessed by 3H-thymidine uptake. Celecoxib at 50, 75 and 100 mM induced apoptosis in EEC from controls (P < 0.05, P < 0.001 and P < 0.001) and patients with endo-metriosis (P < 0.001, P < 0.001 and P < 0.01), as revealed by the Acridine Orange–Ethidium Bromide technique. Western blot analysis showed that celecoxib was effective at increasing COX-2 protein at 100 mM in EEC from endo-metriosis patients (P < 0.05). In EEC from endometriosis patients, celecoxib at 25, 50 and 100 mMwas also effective in reducing COX-2 activity, reflected in the reduction of prostaglandin E2 (PGE2) synthesis (P < 0.001), and VEGF secretion (P < 0.001; P < 0.05 and P < 0.001), assessed by enzyme-linked immunosorbent assay. Exogenous PGE2 did not reverse celecoxib-induced growth inhibition. CONCLUSIONS: This study suggests a direct effect of celecoxi