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Basic Research

EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer

Prostate Cancer and Prostatic Diseases volume 17, pages 10–17 (2014)Cite this article

Subjects

Abstract

Background:

Non-steroidal anti-inflammatory drugs inhibit the activity of cyclooxygenases (COXs), and their usage reduces the risks associated with prostate cancer. Celecoxib is a selective COX-2 inhibitor and reported to prevent the progression of prostate cancer. However, the mechanisms involved remain unclear. In this study, we investigated the suppression of prostate cancer growth by celecoxib and elucidated the biological relevance of the inhibited pathway in prostate cancer cell lines.

Methods:

Western blotting, quantitative real-time PCR and cell proliferation assay were used to resolve the mechanism of celecoxib in prostate cancer cell line PC3, LNCaP and their derivatives.

Results:

Celecoxib induced apoptosis and downregulated EP2, CREB and androgen receptor (AR). Moreover, EP2 antagonist downregulated CREB as well as COX-2 and AR, resulting in the suppression of cell proliferation. Furthermore, EP2 and CREB knockdown induced AR downregulation, indicating that AR suppression by celecoxib is mediated by EP2/CREB signaling.

Conclusions:

Celecoxib exerts antitumor activity through EP2 signaling regulating AR and COX-2 expression. Furthermore, in addition to celecoxib, therapeutics targeting EP2 may also be promising against prostate cancers.

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Acknowledgements

We thank Dr Dongchon Kang (Kyushu University, Fukuoka, Japan) for helping with the quantitative real-time PCR experiments, and Noriko Hakoda and Eriko Gunshima for their technical assistance.

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Authors and Affiliations

  1. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    E Kashiwagi, M Shiota, A Yokomizo, J Inokuchi & S Naito

  2. Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    T Uchiumi

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  1. E Kashiwagi
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Correspondence to A Yokomizo.

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Kashiwagi, E., Shiota, M., Yokomizo, A. et al. EP2 signaling mediates suppressive effects of celecoxib on androgen receptor expression and cell proliferation in prostate cancer. Prostate Cancer Prostatic Dis 17, 10–17 (2014). https://doi.org/10.1038/pcan.2013.53

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