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Molecular targeting of Bcl-2 overcomes prostate cancer cell adaptation to XIAP gene downregulation

Prostate Cancer and Prostatic Diseases volume 12, pages 34–40 (2009)Cite this article

Abstract

X-linked inhibitor of apoptosis (XIAP) is a suppressor of apoptosis that supports an increased survival and resistance to chemotherapy of human prostate cancer (PCa) cells. Effects of transient (24 h) and chronic (beyond 1 month) downregulation of XIAP in DU145 hormone refractory prostate cancer (HRPC) cells were studied. We found that transient downregulation of XIAP by siRNAs resulted in an increase of apoptosis and a decrease in Bcl-2 levels and sensitized PCa cells to cisplatin. XIAP downregulation by shRNA vector stable transfection led to upregulation of Bcl-2 protein. Our results identify the adaptability of PCa cells to chronic loss of XIAP in part through upregulation of Bcl-2 and indicate that multitargeting approach is the most effective application in the chemotherapy of human HRPC.

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Acknowledgements

This research was supported in part by Grants-in-Aid for Scientific Research (no. 17390435) from the Ministry of Education, Science and Culture, Japan (to Y Tomita).

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Authors and Affiliations

  1. Department of Urology, Yamagata University School of Medicine, Yamagata, Japan

    Y Nakano, V Bilim, K Yuuki, A Muto, T Kato, A Nagaoka & Y Tomita

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  1. Y Nakano
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  2. V Bilim
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  3. K Yuuki
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  4. A Muto
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  5. T Kato
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  6. A Nagaoka
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  7. Y Tomita
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Correspondence to Y Tomita.

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Nakano, Y., Bilim, V., Yuuki, K. et al. Molecular targeting of Bcl-2 overcomes prostate cancer cell adaptation to XIAP gene downregulation. Prostate Cancer Prostatic Dis 12, 34–40 (2009). https://doi.org/10.1038/pcan.2008.27

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