Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo

Charlotte Ngô, Carole Nicco, Mahaut Leconte, Christiane Chéreau, Sylviane Arkwright, S Arkwright, Marie-Cécile Vacher-Lavenu, Marie‐Cécile Vacher‐Lavenu, Bernard Weill, Charles Chapron, Frédéric Batteux
The Journal of Pathology · 2010 · vol. 222(2) , pp. 148–157 · doi:10.1002/path.2756 · PMID:20821752 · W2010952228
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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.

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Condition tags

mesh:D004715endometriosischronic_pelvic_paininfertility

MeSH descriptors

Endometriosis Endometrium Protein Kinase Inhibitors Adult Animals Cell Proliferation Cell Proliferation Cells, Cultured Disease Models, Animal Disease Progression Drug Evaluation, Preclinical Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium Enzyme-Linked Immunosorbent Assay Enzyme-Linked Immunosorbent Assay

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