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Disrupting Y-Box-Binding Protein 1 Function Using OSU-03012 Prevents Endometriosis Progression in In Vitro and In Vivo Models

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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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany

    Cássia G. T. Silveira PhD, Gabriele Marschner, Silke Klocke PhD, Peter Hunold MD, PhD, Frank Köster PhD, Thorben Ahrens MD & Daniela Hornung MD, PhD

  2. École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Geraldine O. Canny PhD

  3. Clinic for Radiology and Nuclear Medicine, University of Lübeck, Lübeck, Germany

    Daniela Hornung MD, PhD

  4. Department of Gynecology and Obstetrics, Diakonissenkrankenhaus Karlsruhe Rüppurr, Diakonissenstr 28, 76199, Karlsruhe, Germany

    Achim Rody MD, PhD

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  1. Cássia G. T. Silveira PhD
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  2. Gabriele Marschner
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  3. Geraldine O. Canny PhD
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Correspondence to Daniela Hornung MD, PhD.

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Silveira, C.G.T., Marschner, G., Canny, G.O. et al. Disrupting Y-Box-Binding Protein 1 Function Using OSU-03012 Prevents Endometriosis Progression in In Vitro and In Vivo Models. Reprod. Sci. 24, 67–76 (2017). https://doi.org/10.1177/1933719116649695

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