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Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis.
Hum Reprod. 2008 Dec; 23(12):2701-8.HR

Abstract

BACKGROUND

Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, also has anti-proliferative properties and pro-apoptotic effects on different in vivo and in vitro models, two actions that may be efficacious in therapy for endometriosis. We evaluated the effects of celecoxib on apoptosis and proliferation, and vascular endothelial growth factor (VEGF) production and COX-2 expression and activity in endometrial epithelial cells (EECs).

METHODS AND RESULTS

Thirty-two endometriosis and 13 control women were included in the study. EECs from eutopic endometrium and control biopsies were cultured with different doses of celecoxib. Celecoxib at 50, 75 and 100 microM (versus vehicle control) inhibited EEC proliferation in cultures from controls (P < 0.05, P < 0.01 and P < 0.01, respectively) and patients with endometriosis (P < 0.05, P < 0.01 and P < 0.01), as assessed by (3)H-thymidine uptake. Celecoxib at 50, 75 and 100 microM induced apoptosis in EEC from controls (P < 0.05, P < 0.001 and P < 0.001) and patients with endometriosis (P < 0.001, P < 0.001 and P < 0.01), as revealed by the Acridine Orange-Ethidium Bromide technique. Western blot analysis showed that celecoxib was effective at increasing COX-2 protein at 100 microM in EEC from endometriosis patients (P < 0.05). In EEC from endometriosis patients, celecoxib at 25, 50 and 100 microM was also effective in reducing COX-2 activity, reflected in the reduction of prostaglandin E(2) (PGE(2)) synthesis (P < 0.001), and VEGF secretion (P < 0.001; P < 0.05 and P < 0.001), assessed by enzyme-linked immunosorbent assay. Exogenous PGE(2) did not reverse celecoxib-induced growth inhibition.

CONCLUSIONS

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.

Authors+Show Affiliations

Instituto de Biología y Medicina Experimental CONICET, Vuelta de Obligado 2490 C1428ADN, Ciudad Autónoma de Buenos Aires, Argentina.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18716040

Citation

Olivares, C, et al. "Effects of a Selective Cyclooxygenase-2 Inhibitor On Endometrial Epithelial Cells From Patients With Endometriosis." Human Reproduction (Oxford, England), vol. 23, no. 12, 2008, pp. 2701-8.
Olivares C, Bilotas M, Buquet R, et al. Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Hum Reprod. 2008;23(12):2701-8.
Olivares, C., Bilotas, M., Buquet, R., Borghi, M., Sueldo, C., Tesone, M., & Meresman, G. (2008). Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Human Reproduction (Oxford, England), 23(12), 2701-8. https://doi.org/10.1093/humrep/den315
Olivares C, et al. Effects of a Selective Cyclooxygenase-2 Inhibitor On Endometrial Epithelial Cells From Patients With Endometriosis. Hum Reprod. 2008;23(12):2701-8. PubMed PMID: 18716040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. AU - Olivares,C, AU - Bilotas,M, AU - Buquet,R, AU - Borghi,M, AU - Sueldo,C, AU - Tesone,M, AU - Meresman,G, Y1 - 2008/08/20/ PY - 2008/8/22/pubmed PY - 2009/1/31/medline PY - 2008/8/22/entrez SP - 2701 EP - 8 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 23 IS - 12 N2 - BACKGROUND: Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, also has anti-proliferative properties and pro-apoptotic effects on different in vivo and in vitro models, two actions that may be efficacious in therapy for endometriosis. We evaluated the effects of celecoxib on apoptosis and proliferation, and vascular endothelial growth factor (VEGF) production and COX-2 expression and activity in endometrial epithelial cells (EECs). METHODS AND RESULTS: Thirty-two endometriosis and 13 control women were included in the study. EECs from eutopic endometrium and control biopsies were cultured with different doses of celecoxib. Celecoxib at 50, 75 and 100 microM (versus vehicle control) inhibited EEC proliferation in cultures from controls (P < 0.05, P < 0.01 and P < 0.01, respectively) and patients with endometriosis (P < 0.05, P < 0.01 and P < 0.01), as assessed by (3)H-thymidine uptake. Celecoxib at 50, 75 and 100 microM induced apoptosis in EEC from controls (P < 0.05, P < 0.001 and P < 0.001) and patients with endometriosis (P < 0.001, P < 0.001 and P < 0.01), as revealed by the Acridine Orange-Ethidium Bromide technique. Western blot analysis showed that celecoxib was effective at increasing COX-2 protein at 100 microM in EEC from endometriosis patients (P < 0.05). In EEC from endometriosis patients, celecoxib at 25, 50 and 100 microM was also effective in reducing COX-2 activity, reflected in the reduction of prostaglandin E(2) (PGE(2)) synthesis (P < 0.001), and VEGF secretion (P < 0.001; P < 0.05 and P < 0.001), assessed by enzyme-linked immunosorbent assay. Exogenous PGE(2) did not reverse celecoxib-induced growth inhibition. CONCLUSIONS: 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. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/18716040/Effects_of_a_selective_cyclooxygenase_2_inhibitor_on_endometrial_epithelial_cells_from_patients_with_endometriosis_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/den315 DB - PRIME DP - Unbound Medicine ER -