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

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

Silveira, Cassia G. T.
•
Marschner, Gabriele
•
Canny, Geraldine O.
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2017
Reproductive Sciences

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 mm(3)) compared to those from the control group (50.5 +/- 6.9 mm(3), 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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Type
research article
DOI
10.1177/1933719116649695
Web of Science ID

WOS:000393666600007

Author(s)
Silveira, Cassia G. T.
Marschner, Gabriele
Canny, Geraldine O.
Klocke, Silke
Hunold, Peter
Koester, Frank
Ahrens, Thorben
Rody, Achim
Hornung, Daniela
Date Issued

2017

Publisher

Sage Publications Inc

Published in
Reproductive Sciences
Volume

24

Issue

1

Start page

67

End page

76

Subjects

endometriosis

•

growth inhibition

•

mouse model

•

OSU-03012

•

YB-1

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
NON-ACADEMIC  
Available on Infoscience
March 27, 2017
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/135979
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