Open Access

Celecoxib, a selective COX‑2 inhibitor, markedly reduced the severity of tamoxifen‑induced adenomyosis in a murine model

  • Authors:
    • Zhixing Jin
    • Xiaoyi Wu
    • Haiou Liu
    • Congjian Xu
  • View Affiliations

  • Published online on: March 6, 2020     https://doi.org/10.3892/etm.2020.8580
  • Pages: 3289-3299
  • Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to evaluate the effects of the selective cyclooxygenase (COX)‑2 inhibitor celecoxib on the development of uterine adenomyosis in mice. ICR neonatal mice were first exposed to tamoxifen to establish a mouse model of adenomyosis. Following 60 days of celecoxib treatment, pathological formation of adenomyosis lesions and the depth of myometrial infiltration were evaluated using hematoxylin and eosin staining. To examine thermal pain modulation in mice, a hotplate test was conducted every 15 days from postnatal day 30 onwards. Immunohistochemistry was performed to assess the expression of aromatase P450, N‑cadherin, E‑cadherin, COX‑2 and cluster of differentiation 31, whereas the levels of estrogen were analyzed in uterine tissue homogenates using ELISA. Masson trichrome staining was performed to assess the extent of fibrosis in the uterus. Celecoxib treatment significantly inhibited the depth of infiltration into the myometrium, resulting in significantly reduced disease severity. Treatment with high doses of celecoxib significantly prolonged thermal response latency. Following celecoxib treatment, the expression of E‑cadherin was significantly increased whereas the expression of N‑cadherin was significantly decreased. Concomitantly, the extent of fibrosis was also reduced following celecoxib treatment. Uterine tissue homogenates isolated from mice treated with both high and low doses of celecoxib exhibited lower concentrations of estrogen and decreased expression of aromatase P450. These observations suggest that celecoxib reduces adenomyosis severity by suppressing estrogen production in the uterus, reversing epithelial‑mesenchymal transition and relieving fibrosis. Taken together, the results of the present study support the potential use of celecoxib, a selective COX‑2 inhibitor, for the treatment of adenomyosis.

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May 2020
Volume 19 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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APA
Jin, Z., Wu, X., Liu, H., & Xu, C. (2020). Celecoxib, a selective COX‑2 inhibitor, markedly reduced the severity of tamoxifen‑induced adenomyosis in a murine model. Experimental and Therapeutic Medicine, 19, 3289-3299. https://doi.org/10.3892/etm.2020.8580
MLA
Jin, Z., Wu, X., Liu, H., Xu, C."Celecoxib, a selective COX‑2 inhibitor, markedly reduced the severity of tamoxifen‑induced adenomyosis in a murine model". Experimental and Therapeutic Medicine 19.5 (2020): 3289-3299.
Chicago
Jin, Z., Wu, X., Liu, H., Xu, C."Celecoxib, a selective COX‑2 inhibitor, markedly reduced the severity of tamoxifen‑induced adenomyosis in a murine model". Experimental and Therapeutic Medicine 19, no. 5 (2020): 3289-3299. https://doi.org/10.3892/etm.2020.8580