In-vitro evaluation of a selective cyclooxygenase-2 inhibitor, celecoxib, as a therapeutic alternative for endometriosis.

OLIVARES C; BILOTAS M; BUQUET R; BORGHI M; SUELDO C; TESONE M; MERESMAN G

Huerta Grande, Córdoba

Congreso; I Reunión conjunta de Sociedades de Biología de la República Argentina; 2007

Sociedad Argentina de Biología

Celecoxib is a specific inhibitor of COX-2. In cell lines from different types of cancer, as in animal models, it has been demonstrated that celecoxib inhibits cell proliferation, induces apoptosis and stimulates the expression of COX-2. The purpose of the present study was to investigate the effect of celecoxib on cell proliferation, apoptosis, expression of COX-2 and levels of VEGF and PGE2 on endometrial epithelial cell cultures (EEC) from EDT patients EDT and controls. The EEC were performed from eutopic endometrium biopsies from 13 control women and 27 patients with untreated EDT, and were stimulated with different doses of celecoxib. Cell proliferation was evaluated by 3H-thymidine uptake and apoptosis, by the acridine orange-ethidium bromide technique. Expression of COX-2 was evaluated by Western blot and the levels of VEGF and PGE2, in the culture supernatants, were measured by Elisa. Celecoxib 50, 75 and 100mM diminished significantly cell proliferation and enhanced apoptosis, in EEC from patients with EDT and controls. Likewise, 100 mM of celecoxib significantly induced expression of COX-2 (p<0.05 vs. basal without celecoxib) in cultures from patients with EDT. Furthermore, concentrations of 25, 50 and 100mM of celecoxib inhibited secretion of VEGF (p<0.001, p<0.05 and p<0.001 vs. basal, respectively) and PGE2 (p<0.001 vs. basal in all cases) in cell cultures from patients with EDT. Our results show that celecoxib is an effective inhibitor of cell proliferation, enhances apoptosis, induces COX-2 expression and inhibits the secretion of the inflammatory and pro-angiogenic molecules PGE2 and VEGF.