A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model

Machado, Daniel Escorsim; Berardo, Plínio Tostes; Landgraf, Richardt Gama; Fernandes, Patrícia Dias; Palmero, Celia Yelimar; Miranda-Alves, Leandro; Abrão, Maurício Simões; Nasciutti, Luiz Eurico

doi:10.1016/j.fertnstert.2009.11.037

Cited by 70 publications

(45 citation statements)

References 38 publications

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“…Our group has demonstrated that selective inhibition of COX-2 activity with celecoxib reduces the proliferation rate of endometrial epithelial cells as well as it augments their apoptosis levels both in vitro and in vivo (Olivares et al 2008. Similar results were obtained by other investigators demonstrating that the inhibition of COX-2 activity has antiproliferative, proapoptotic, and antiangiogenic effects in several in vivo and in vitro cancer models (Gupta et al 2004, Basu et al 2005, Dandekar et al 2005, Barnes et al 2007 and in other models of endometriosis (Dogan et al 2004, Laschke et al 2007, Machado et al 2010. Moreover, a COX-2 inhibitor has been used in a pilot study evaluating pain response in endometriosis patients with good results (Cobellis et al 2004).…”

Section: Introductionsupporting

confidence: 82%

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

et al. 2013

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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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Section: Introductionsupporting

confidence: 82%

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

et al. 2013

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“…Hull et al [20] reported that nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis. Machado et al [21] found out that a selective COX-2 inhibitor suppresses the growth of endometriosis in a rat model. They stated that the use of COX-2 selective inhibitors could be effective in suppressing the establishment and growth of endometriosis, partially via their antiangiogenic activity.…”

Section: Discussionmentioning

confidence: 99%

“…Dexketoprofen trometamol is licensed in a number of countries around the world. Oral dexketoprofen was approved in the European countries through a mutual recognition procedure on February 13, 1998, and the injectable formulation on October 25, 2002 [21]. In the present study, we investigated the effects of this drug on experimentally induced endometriotic cysts in rats (fig.…”

Section: Discussionmentioning

confidence: 99%

Regression of Experimentally Induced Endometriosis with a New Selective Cyclooxygenase-2 Enzyme Inhibitor

Kilico

Kökçü²,

Kefeli³

et al. 2013

Gynecol Obstet Invest

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Background: Cyclooxygenase-2 (COX-2) levels increase in women with endometriosis. COX-2, via increasing prostaglandin E₂, contributes to an increase in vascular endothelial growth factor. In this way, COX-2 may contribute to the progression and continuity of endometriosis. We investigated the effect of dexketoprofen trometamol, a new selective COX-2 enzyme inhibitor, on experimentally induced endometriotic cysts. Methods: Experimental endometriotic cysts were created in 60 adult female Wistar albino rats. The rats were randomized to 2 equal groups, a control (group Con) and a dexketoprofen (group Dex) group. Six weeks later, cyst volumes were measured as in vivo (volume 1). Following volume 1 measurement, for 4 weeks group Con received 0.1 ml distilled water; group Dex received 0.375 mg dexketoprofen trometamol/0.1 ml distilled water, intramuscularly, twice a day. At the end of administration, the cyst volumes were remeasured (volume 2), and the cysts totally excised and weighed. Glandular (GT) and stromal tissues (ST) and natural killer (NK) cell contents in the cyst wall were scored. Results: NK cell content and volume 1 were not different between the 2 groups. Volume 2, cyst weight, and GT and ST contents in group Dex were significantly lower than those in group Con. Conclusion: Dexketoprofen trometamol significantly reduced the development of experimentally induced endometriotic cysts both macroscopically and microscopically.

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“…Other specific COX-2 inhibitors-rofecoxib, NS-398, and parecoxib-also have been demonstrated to statistically significantly reduce the size of endometriosislike implants, inducing their atrophy and regression (84,85,121). The effect of rofecoxib was equivalent to that obtained with a GnRH agonist (121).…”

Section: Anti-inflammatory Agentsmentioning

confidence: 96%