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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.
Original language | English |
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Journal | Reproductive Sciences |
Volume | 24 |
Issue number | 1 |
Pages (from-to) | 67-76 |
Number of pages | 10 |
ISSN | 1933-7191 |
DOIs | |
Publication status | Published - 01.01.2017 |
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Dive into the research topics of 'Disrupting Y-Box-Binding Protein 1 Function Using OSU-03012 Prevents Endometriosis Progression in In Vitro and in Vivo Models'. Together they form a unique fingerprint.Projects
- 1 Finished
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The YB-1 downstream pathways- diagnostic and therapeutic approaches for endometriosis -
Hornung, D. & Agic, A.
01.11.12 → 31.10.18
Project: DFG Projects › DFG Individual Projects