Regulación del crecimiento del tejido endometrial eutópico en respuesta a nuevas alternativas terapéuticas propuestas para tratar la endometriosis.

OLIVARES C; MERESMAN G

Anales de la Fundación Alberto J Roemmers

Fundacion Roemmers

Año: 2011; p. 211 - 223

BACKGROUND: Anastrozole is an aromatase P450 inhibitor, rosiglitazone is a peroxisome proliferator-activated receptor (PPAR)γ agonist and celecoxib is a selective cyclooxygenase (COX)-2 inhibitor, both of which have been described to have antiproliferative, antiapoptotic and antiangiogenic effects in vitro and in vivo. We evaluated the effects of these drugs separately or combined on the implantation and growth of endometriotic implants in a murine model of endometriosis. METHODS AND RESULTS: BALB/c mice underwent surgery for endometriosis induction. After 28 days of treatment with: 1) vehicle, celecoxib, anastrozole or both drugs simultaneously or 2) vehicle, celecoxib, rosiglitazone or both drugs simultaneously, mice were sacrificed and the number of lesions established was counted, measured and fixed. Celecoxib and the combined treatment with rosiglitazone significantly reduced the mean number of lesions established per mouse (p<0.05 vs. Control). In addition, celecoxib, rosiglitazone (p<0.05 vs. Control) and celecoxib + rosiglitazone (p<0.001 vs. Control) diminished implant volume. Immunohistochemistry of PCNA revealed that cell proliferation within the implants was significantly reduced by the treatments: celecoxib (p<0.01 vs. Control); rosiglitazone, celecoxib + rosiglitazone (p<0.001 vs. Control) and anastrozole (p<0.05 vs. Control). TUNEL assay was performed to evaluate apoptosis and all treatments enhanced the percentage of apoptotic cells in the implant (p<0.05 vs. Control). Finally, vascular density was assessed by immunohistochemistry of CD 34 and celecoxib, rosiglitazone (p<0.05 vs. Control); and celecoxib + rosiglitazone (p<0.01 vs. Control) diminished the vascularized area. CONCLUSIONS: The results presented in this work are promising and reveal that celecoxib and rosiglitazone, combined or separately, have a beneficial effect on endometriotic growth by inhibiting cell proliferation and vascular density and increasing cell apoptosis.