Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo
Abstract
Endometriosis affects 6–10% of women in their reproductive years, causing chronic pelvic pain and infertility. Its pathogenesis remains poorly understood and current treatments, based on hormonal therapy or surgery, are often insufficient. The purpose of our study was to investigate the role of the ERK pathway in the development of endometriosis and to test the effects of protein kinase inhibitors on the proliferation of endometriotic cells in vitro and in vivo. We studied ex vivo human endometrial and endometriotic cells in culture. Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. The ERK pathway was explored by western blot on cell lysates and by ELISA on total crushed specimens of endometrium. Cells in culture were treated with A771726, PD98059, and U0126. Human endometriotic lesions were implanted in nude mice. Mice were treated with A771726, leflunomide, PD98059, U0126 or PBS during 2 weeks before sacrifice and extraction of the endometriotic implants for histological examination. We found that the ERK pathway was significantly activated in endometriotic cells and in endometrial cells from patients with endometriosis compared to endometrial cells of control patients, both by ELISA and by western blot. This phenomenon was associated with an increased proliferation of endometriotic cells compared to endometrial cells. Treating endometriotic cells with A771726, PD98059 or U0126 abrogated the phosphorylation of ERK and significantly decreased the cellular proliferation in vitro. In vivo, A771726, leflunomide, PD98059, and U0126 controlled the growth of endometriotic implants in the mouse model of endometriosis. Our study shows that protein kinase inhibitors could be new candidates to treat endometriosis. However, further studies are needed to evaluate their effects and tolerability in humans. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Protein kinase inhibitors could be considered as new candidates to treat endometriosis.
“Based on these results, it is suggested that protein kinase inhibitors could be considered as new candidates to treat endometriosis; however, further studies are needed to evaluate their effects and tolerability in humans.”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [76]
In vivo A771726, leflunomide, PD98059, and U0126 modulated the growth of endometriotic implants in a mouse model of endometriosis.
“In vivo A771726, leflunomide, PD98059, and U0126 modulated the growth of endometriotic implants in a mouse model of endometriosis.76”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [76]
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Self-citation
- Authors
- Ngô, C., Nicco, C., Leconte, M., Chéreau, C., Arkwright, S., Vacher‐Lavenu, M., Weill, B., Chapron, C., & Batteux, F.
- Affiliations
- Hôpital Cochin (FR)
- Corresponding author
- Batteux, Frédéric
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2010-09
- Volume
- 222
- Issue
- 2
- Pages
- 148-157
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2010952228
- Cited by
- 78
- References
- 49
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 10 · 2014: 2 · 2013: 6 · 2012: 6
- FWCI
- 6.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- endometriosis, protein kinase inhibitors, ERK signaling, A771726, PD98059, U0126, leflunomide, endometriotic implants, ERK1/2 phosphorylation, mouse model of endometriosis
- MeSH terms
- Adult, Animals, Cells, Cultured, Disease Models, Animal, Drug Evaluation, Preclinical, Endometriosis, Endometrium, Enzyme-Linked Immunosorbent Assay, Epithelial Cells, Female, Humans, Mice, Nude, Stromal Cells, Disease Progression, MAP Kinase Signaling System, Protein Kinase Inhibitors, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Mice
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