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- Title
Inhibition of MAPK and VEGFR by Sorafenib Controls the Progression of Endometriosis.
- Authors
Leconte, Mahaut; Santulli, Pietro; Chouzenoux, Sandrine; Marcellin, Louis; Cerles, Olivier; Chapron, Charles; Dousset, Bertrand; Batteux, Frédéric
- Abstract
Introduction: Sorafenib is a strong multikinase inhibitor targeting 2 different pathways of endometriosis pathogenesis: RAF kinase and vascular endothelial growth factor receptor (VEGFR). We investigate whether Sorafenib could control the growth of endometriotic lesions both in vitro and in vivo. Methods: Stromal primary cells were extracted from endometrial and endometriotic biopsies from patients with (n = 10) and without (n = 10) endometriosis. Proliferation, apoptosis, mitogen-activated protein kinases, and VEGFR-2 autophosphorylation were explored with and without Sorafenib treatment. Human endometriotic lesions were implanted in 30 nude mice randomized according to Sorafenib or placebo treatment. Results: Treating endometriotic cells with Sorafenib abrogated the phosphorylation of extracellular signal-regulated kinase in stromal cells of women with endometriosis compared to controls. In addition, this study highlights the antiangiogenic role of Sorafenib which translates as a decreased phosphorylated VEGFR-2–VEGFR-2 ratio in endometriosis. Using a xenogenic mouse model of endometriosis, we confirmed that Sorafenib regulates the endometriosis activity in vivo by targeting endometriosis-related proliferation and inflammation. Conclusion: Our data suggest that Sorafenib controls the growth of endometriotic lesions in vitro and in vivo.
- Subjects
VASCULAR endothelial growth factors; ENDOMETRIOSIS; ENDOMETRIUM; FEMALE reproductive organ diseases; PELVIC diseases; GROWTH factors; ANGIOPOIETIN-like proteins
- Publication
Reproductive Sciences, 2015, Vol 22, Issue 9, p1171
- ISSN
1933-7191
- Publication type
Article
- DOI
10.1177/1933719115592708