Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis

Olivares, Carla Noemí; Bilotas, Mariela Andrea; Buquet, Ricardo; Borghi, M; Sueldo, Carlos; Tesone, Marta; Meresman, Gabriela Fabiana

doi:10.1093/humrep/den315

Cited by 67 publications

(53 citation statements)

References 48 publications

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“…Celecoxib has been shown to have anti-proliferative and pro-apoptotic effects over endometrial epithelial cells in culture obtained from biopsies of women with and without endometriosis; it was also effective in diminishing COX-2 expression, reducing the synthesis of VEGF and PGE 2 (Olivares et al, 2008). Similar results had previously been achieved in various cancer models (Basu et al, 2005;Chun & Surh, 2004).…”

Section: Pge 2 Synthesis Inhibition and The Control Over Endometriosisupporting

confidence: 73%

Involvement of Prostaglandins in the Pathophysiology of Endometriosis

Meresman¹,

Olivares²

2012

Endometriosis - Basic Concepts and Current Research Trends

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Section: Pge 2 Synthesis Inhibition and The Control Over Endometriosisupporting

confidence: 73%

Involvement of Prostaglandins in the Pathophysiology of Endometriosis

Meresman¹,

Olivares²

2012

Endometriosis - Basic Concepts and Current Research Trends

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“…Particularly, high concentration of PGE 2 has been found in the peritoneal fluid of patients with endometriosis, primarily provided by activated macrophages and the endometriotic lesions (Wu et al 2010). 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.…”

Section: Introductionmentioning

confidence: 94%

“…We and others have studied the involvement of cyclooxygenase-2 (COX-2) in this pathology (Matsuzaki et al 2004, Banu et al 2008, Olivares et al 2008, 2011, which has been described to be overexpressed not only in eutopic and ectopic endometrium from endometriosis patients (Ota et al 2001, Fagotti et al 2004) but also in a wide variety of cancers (Mendes et al 2009, Ghosh et al 2010, Wang et al 2010. Selective COX-2 inhibitors are a special class of nonsteroidal antiinflammatory drugs that were developed to treat pain and inflammation without inhibiting COX-1, thus sparing the gastrointestinal system (Wadman 2007).…”

Section: Introductionmentioning

confidence: 99%

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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“…Peritoneal fluid concentrations of prostaglandin E 2 (PGE 2 ) are higher in women with endometriosis, and this increased PGE 2 plays an important role in survival and growth of endometriosis lesions (6)(7)(8)(9). Inhibition of PGE 2 biosynthesis impedes growth of endometriosis (9) and chronic pelvic pain in women (7), and decreases growth of endometriosis lesions in animal models (8).…”

mentioning

confidence: 99%

Molecular and preclinical basis to inhibit PGE ₂ receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

Arosh

Lee

Balasubbramanian

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Endometriosis is a debilitating, estrogen-dependent, progesteroneresistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E 2 (PGE 2 ) are higher in women with endometriosis, and this increased PGE 2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE 2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis.PGE2 signaling | endometriosis | pelvic pain | pain pathways | infertility

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Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis

Abstract: This study suggests a direct effect of celecoxib on reduction of endometrial growth and supports further research on selective COX-2 inhibition as a novel therapeutic modality in endometriosis.

Cited by 67 publications

References 48 publications

Involvement of Prostaglandins in the Pathophysiology of Endometriosis

Involvement of Prostaglandins in the Pathophysiology of Endometriosis

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

Molecular and preclinical basis to inhibit PGE ₂ receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

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Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis

Abstract: This study suggests a direct effect of celecoxib on reduction of endometrial growth and supports further research on selective COX-2 inhibition as a novel therapeutic modality in endometriosis.

Cited by 67 publications

References 48 publications

Involvement of Prostaglandins in the Pathophysiology of Endometriosis

Involvement of Prostaglandins in the Pathophysiology of Endometriosis

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

Molecular and preclinical basis to inhibit PGE 2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

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Product

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Molecular and preclinical basis to inhibit PGE ₂ receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis