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

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.

Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions

“…The present study demonstrates that a combination therapy with telmisartan and the COX‐2 inhibitor parecoxib is more effective in the treatment of endometriotic lesions than treatment with telmisartan alone. This novel result is in line with the finding that (i) telmisartan and other related anti‐hypertensive drugs, such as losartan, suppress lesion formation in different murine endometriosis models (Nenicu et al, ; Cakmak et al, ) and that (ii) COX‐2 represents a promising target for an analgesic, anti‐angiogenic and anti‐inflammatory endometriosis therapy (Cobellis et al, ; Ozawa et al, ; Laschke et al, ; Machado et al, ; Olivares et al, ; Kilico et al, ). In fact, telmisartan activates PPAR‐γ, which has been shown to enhance COX‐2 expression in different cell types (Meade et al, ; Ackerman et al, ).…”

“…This is a surprising finding considering the fact that COX‐2 has been suggested to promote the development and progression of endometriosis (Buchweitz et al, ; Banu et al, ; Wu et al, ). In addition, several studies have reported that selective COX‐2 inhibitors have beneficial therapeutic effects on endometriotic lesion formation and endometriosis‐associated pain (Cobellis et al, ; Ozawa et al, ; Laschke et al, ; Machado et al, ; Olivares et al, ; Kilico et al, ). Accordingly, in the present study we speculated that a combination therapy with telmisartan and a COX‐2 inhibitor may be even more effective in the treatment of endometriosis than treatment with telmisartan alone.…”

Endometriosis — insights into a multifaceted entity

“…In a rat endometriosis model, bevacizumab, VEGF-neutralizing monoclonal antibody, was shown to increase apoptosis [275]. Other drugs with anti-angiogenic effects confirmed in experimental endometriosis are celecoxib, a COX-2 inhibitor [276], and non-toxic fumagillin analogs, semisynthetic derivatives of a natural antibiotic, Aspergillus fumigatus [274]. The results of these Tumor suppressor ARID1A ± BAF250a mutation [94,95,96,105,209,[230][231][232][233] expressed [105,233] expressed [94,95,96,105,209,[230][231][232] PTEN somatic mutations [87-89, 93, 227, 228, 234] expressed [88,89,93,227,228] expressed [87,88,227,228,234] PIK3CA mutations [96,104,207] early event in endometriosis transformation [104] expressed [96,104,207] TP53 [90-92, 107, 213, 228, 229] expressed (late stages) [91,92,107,…”

Endometriosis: alternative methods of medical treatment

“…A study in mice compared the response in endometriotic lesions to celecoxib, anastrozole, or their combination 66. Celecoxib was the only treatment that significantly reduced the number of lesions established per mouse, lesion size, and vascularized area.…”