title: Disrupting Y-Box-Binding Protein 1 Function Using OSU-03012 Prevents Endometriosis Progression in In Vitro and In Vivo Models.
abstract: The objective of the present study was to test the ability of OSU-03012 (2-amino-N-[4-[5-phenanthren-2-yl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]acetamide), a novel and potent celecoxib-derivative, to impair endometriosis progression in in vitro and in vivo models based on its ability to indirectly block Y-box-binding protein 1 (YB-1) function. 12Z human endometriotic epithelial cells and sexually mature female C57BL/6J mice were treated with OSU-03012. Cellular proliferation was quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid assay. Expression of YB-1 and phosphorylated YB-1 in 12Z cells and endometriotic lesions was evaluated by Western blotting and immunohistochemistry (IHC). The IHC for proliferating cell nuclear antigen was performed. OSU-03012 treatment resulted in decreased YB-1 and its phosphorylated form in both in vitro and in vivo models. Endometriotic lesion size was significantly reduced in OSU-03012-treated mice (27.6 ± 4.0 mm3) compared to those from the control group (50.5 ± 6.9 mm3, P < .0001). A significant reduction in endometriotic epithelial cell proliferation was observed in endometriotic lesions exposed to OSU-03012 treatment ( P = .0346). In conclusion, targeting YB-1 via OSU-03012 showed a potent antiproliferative effect on endometriotic epithelial cells in vitro and in a mouse model of disease.
authors.affiliation: 1 Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany.
authors.forename: Cássia G T
authors.initials: CGT
authors.lastname: Silveira
authors.affiliation: 1 Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Marschner
authors.affiliation: 2 École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Geraldine O
authors.initials: GO
authors.lastname: Canny
authors.affiliation: 1 Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Klocke
authors.affiliation: 3 Clinic for Radiology and Nuclear Medicine, University of Lübeck, Lübeck, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hunold
authors.affiliation: 1 Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Köster
authors.affiliation: 1 Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany.
authors.forename: Thorben
authors.initials: T
authors.lastname: Ahrens
authors.affiliation: 1 Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Rody
authors.affiliation: 1 Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany.|4 Department of Gynecology and Obstetrics, Diakonissenkrankenhaus Karlsruhe Rüppurr, Karlsruhe, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hornung
keywords: OSU-03012; YB-1; endometriosis; growth inhibition; mouse model