Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model.
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.
Edamura
K
K
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Nasu
Y
Y
Takaishi
M
M
Kobayashi
T
T
Abarzua
F
F
Sakaguchi
M
M
Kashiwakura
Y
Y
Ebara
S
S
Saika
T
T
Watanabe
M
M
Huh
N-H
NH
Kumon
H
H
D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000235:genetics*; D045744:Cell Line, Tumor; D018925:Chemokines; D015552:Injections, Intralesional; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins