CICLOOXYGENASE-2 (COX-2) INHIBITOR CELECOXIB INDUCES APOPTOSIS AND INHIBITS CELL GROWTH AND VEGF LEVELS IN ENDOMETRIAL EPITHELIAL CELLS (EEC) FROM PATIENTS WITH ENDOMETRIOSIS (EDT).

MERESMAN GABRIELA; OLIVARES CARLA; BILOTAS MARIELA; BUQUET RICARDO; SUELDO CARLOS; TESONE MARTA

Buenos Aires

Congreso; VIII Jornadas Multidisciplinarias de la Sociedad Argentina de Biología.; 2006

CICLOOXYGENASE-2 (COX-2) INHIBITOR CELECOXIB INDUCES APOPTOSIS AND INHIBITS CELL GROWTH AND VEGF LEVELS IN ENDOMETRIAL EPITHELIAL CELLS (EEC) FROM PATIENTS WITH ENDOMETRIOSIS  (EDT). Meresman G1, Olivares C1, Bilotas M1, Buquet R2, Sueldo C3, Tesone M1. 1Instituto de Biología y Medicina Experimental. 2Hosp. de Clínicas. 3CEGYR Bs. As., Argentina. meresman@dna.uba.ar There is room for improvement in the medical therapy of EDT. Celecoxib, strongly suppresses cell proliferation and induces apoptosis in different tumor cell lines and in oncogenic animal models. The purpose of this study was to evaluate the effect of celecoxib on cell proliferation, apoptosis and VEGF levels in EEC cultures from patients with EDT and controls. Primary cultures of the EEC were performed from biopsies of eutopic endometrial tissue of 14 patients with EDT and 10 controls. EEC were treated with celecoxib in different doses. Percentages of apoptotic cells (%Ap) were evaluated using the acridine orange-ethidium br. technique and cell proliferation, by 3H-thymidine incorporation. VEGF levels were measured by ELISA in the supernatants of celecoxib treated EEC. Celecoxib 50, 75, and 100 mM induced apoptosis and inhibited cell proliferation in EEC from patients with EDT and controls (table I). Celecoxib 25, 50 and 100 mM decreased VEGF levels in EEC (p<0.001, 0.05 and 0.001 respect vs. basal). Table I Celecoxib (mM) 10 20 25 40 50 75 100 CONTROLS Cell prolifer. (% of basal) 86.6±3.7 80.2±4.0 67.7±5.6 64.2±4.1 58.0±5.8* 43.7±11.0 ** 36.20±8.3 *** %Ap (fold increase) 1.6±0.22 1.6±0.19 1.4±0.2 2.2±0.45 2.5±0.44* 2.7±0.3 *** 3.1±0.5 *** EDT Cell prolifer. (% of basal) 84.3±4.0 79.0±3.2 64.9±6.8 68.3±3.0 55.0±4.3* 37.6±4.8 ** 34.0±3.5 ** %Ap (fold increase) 1.4±0.23 1.2±0.34 1.0±0.31 2.2±0.27 2.8±0.47 *** 3.3±0.6 *** 3.1±0.8 ** Mean ± SEM, *p<0.05, **p<0.01, ***p<0.001 vs. basal Conclusions: Celecoxib produced a significant and positive effect on apoptosis and cell proliferation on EEC and showed an antiangiogenic activity. These findings support the further investigation of COX-2 inhibitors as a treatment option in EDT.