Anastrozole and celecoxib for endometriosis treatment, good to keep them apart?

Carla Noemí Olivares, Carla N Olivares, Olivares CN, Mariela A Bilotas, Mariela Bilotas, Analía Gabriela Ricci, Analía G Ricci, Rosa Inés Barañao, Barañao RI, Gabriela Meresman, Gabriela F Meresman
Reproduction (Cambridge, England) · 2012 · vol. 145(2) , pp. 119–126 · doi:10.1530/rep-12-0386 · PMID:23148086 · W2120282574
article OA: bronze CC0 ⤵ 13 in-corpus citations
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Celecoxib alone reduced endometriotic lesion number, size, and vascularization while increasing apoptosis, but combining it with anastrozole reversed these beneficial effects in a mouse model.

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Abstract

Endometriosis is a benign gynecological disease. Cyclooxygenase-2 (COX-2) and aromatase proteins have been shown to be overexpressed in eutopic endometrium from women suffering from this disease compared to disease-free women. Furthermore, inhibition of these molecules individually was demonstrated to have antiproliferative and proapoptotic effects both in vitro and in vivo in several models. In this study, the effect of combining celecoxib, a selective COX-2 inhibitor, and anastrozole, an aromatase inhibitor, on the implantation and growth of endometriotic like lesions in a murine model of endometriosis was evaluated. Endometriosis was surgically induced in female BALB/c mice. After 28 days of treatment with celecoxib, anastrozole, or their combination, animals were killed and lesions were counted, measured, excised, and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for assessment of cell proliferation and vascularization. TUNEL technique was performed for apoptosis evaluation. Celecoxib was the only treatment to significantly reduce the number of lesions established per mouse, their size and vascularized area. In addition, cell proliferation was significantly diminished and apoptosis was significantly enhanced by both individual treatments. When the therapies were combined, they reversed their effects. These results confirm that celecoxib and anastrozole separately decrease endometriotic growth, but when combined they might have antagonizing effects.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Nitriles Peritoneal Diseases Pyrazoles Sulfonamides Triazoles Uterine Diseases Anastrozole Animals Aromatase Inhibitors Aromatase Inhibitors Aromatase Inhibitors Aromatase Inhibitors Celecoxib Cyclooxygenase 2 Inhibitors Cyclooxygenase 2 Inhibitors Cyclooxygenase 2 Inhibitors Cyclooxygenase 2 Inhibitors Drug Combinations Drug Evaluation, Preclinical

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