Inhibition of MAPK and VEGFR by Sorafenib Controls the Progression of Endometriosis. (September 2015)

• Record Type: Journal Article
• Authors: Leconte, Mahaut; Santulli, Pietro; Chouzenoux, Sandrine; Marcellin, Louis; Cerles, Olivier; Chapron, Charles; Dousset, Bertrand; Batteux, Frédéric
• Is Part Of: Reproductive sciences. Volume 22:Number 9(2015:Sep.)
• Page Start: 1171
• Page End: 1180
• Publication Date: 2015-09
• Subjects: sorafenib -- endometriosis -- MAPK -- RAF kinase -- VEGFR-2; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719115592708
• Languages: English
• ISSNs: 1933-7191

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.