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Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo.
J Pathol. 2010 Oct; 222(2):148-57.JP

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.

Authors+Show Affiliations

Université Paris Descartes, Faculté de Médecine, EA 1833 AP-HP Hôpital Cochin, 75679 Paris Cedex 14, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20821752

Citation

Ngô, Charlotte, et al. "Protein Kinase Inhibitors Can Control the Progression of Endometriosis in Vitro and in Vivo." The Journal of Pathology, vol. 222, no. 2, 2010, pp. 148-57.
Ngô C, Nicco C, Leconte M, et al. Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo. J Pathol. 2010;222(2):148-57.
Ngô, C., Nicco, C., Leconte, M., Chéreau, C., Arkwright, S., Vacher-Lavenu, M. C., Weill, B., Chapron, C., & Batteux, F. (2010). Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo. The Journal of Pathology, 222(2), 148-57. https://doi.org/10.1002/path.2756
Ngô C, et al. Protein Kinase Inhibitors Can Control the Progression of Endometriosis in Vitro and in Vivo. J Pathol. 2010;222(2):148-57. PubMed PMID: 20821752.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo. AU - Ngô,Charlotte, AU - Nicco,Carole, AU - Leconte,Mahaut, AU - Chéreau,Christiane, AU - Arkwright,Sylviane, AU - Vacher-Lavenu,Marie-Cécile, AU - Weill,Bernard, AU - Chapron,Charles, AU - Batteux,Frédéric, PY - 2010/9/8/entrez PY - 2010/9/8/pubmed PY - 2010/10/19/medline SP - 148 EP - 57 JF - The Journal of pathology JO - J. Pathol. VL - 222 IS - 2 N2 - 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. SN - 1096-9896 UR - https://www.unboundmedicine.com/medline/citation/20821752/Protein_kinase_inhibitors_can_control_the_progression_of_endometriosis_in_vitro_and_in_vivo_ L2 - https://doi.org/10.1002/path.2756 DB - PRIME DP - Unbound Medicine ER -