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

• DOI: 10.1038/sj.cgt.7701071
• Publication Date: 2007-06-29T08:43:49Z
• Authors: K Edamura; Y Nasu; M Takaishi; T Kobayashi; F Abarzua; M Sakaguchi; Y Kashiwakura; S Ebara; T Saika; M Watanabe; N-H Huh; H Kumon
• Keywords: Male; 0301 basic medicine; Prostatic Neoplasms; Apoptosis; Injections, Intralesional; Transfection; Models, Biological; Adenoviridae; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cell Line, Tumor; Animals; Intercellular Signaling Peptides and Proteins; Chemokines; Neoplasm Metastasis; Cell Division; Adaptor Proteins, Signal Transducing

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.