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

Cássia G.T. Silveira, Gabriele Marschner, Geraldine O. Canny, Silke Klocke, Peter Hunold, Frank Köster, Thorben Ahrens, Achim Rody, Daniela Hornung*

*Corresponding author for this work

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.

Original languageEnglish
JournalReproductive Sciences
Volume24
Issue number1
Pages (from-to)67-76
Number of pages10
ISSN1933-7191
DOIs
Publication statusPublished - 01.01.2017

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