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Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model

Cancer Gene Therapy volume 14, pages 765–772 (2007)Cite this article

Abstract

We had previously reported that REIC/Dkk-3, a member of the Dickkopf (Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene (Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.

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Acknowledgements

This work was supported by a Scientific Research Grant from the Japan Society for the Promotion of Science (B(2) 15390491; Y Nasu) and a Health and Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare (Third Term Comprehensive Control Research for Cancer; H Kumon). We thank Genofunction, Co. Ltd for providing an adenovirus vector carrying REIC/Dkk-3, and Yuka Matono and Katsuo Ohno for their technical assistance.

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Authors and Affiliations

  1. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    K Edamura, Y Nasu, T Kobayashi, F Abarzua, S Ebara, T Saika, M Watanabe & H Kumon

  2. Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    M Takaishi, M Sakaguchi & N-H Huh

  3. Center for Gene and Cell Therapy, Okayama University Hospital, Okayama, Japan

    Y Kashiwakura

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  1. K Edamura
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Correspondence to Y Nasu.

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Edamura, K., Nasu, Y., Takaishi, M. et al. Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model. Cancer Gene Ther 14, 765–772 (2007). https://doi.org/10.1038/sj.cgt.7701071

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