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ID 48076
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Thumnail 66_1_7.pdf 2.06 MB
Author
Kawauchi, Keiichiro
Huang, Peng
Sasaki, Kasumi
Ochiai, Kazuhiko
Huh, Nam-ho
Abstract
The preclinical safety and therapeutic efficacy of adenoviral vectors that express the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) was examined for use in prostate cancer gene therapy. The Ad-human (h) and mouse (m) REIC were previously demonstrated to induce strong anti-cancer effects in vitro and in vivo, and we herein report the results of two in vivo studies. First, intra-tumor Ad-hREIC administration was examined for toxicity and therapeutic effects in a subcutaneous tumor model using the PC3 prostate cancer cell line. Second, intra-prostatic Ad-mREIC administration was tested for toxicity in normal mice. The whole-body and spleen weights, hematological and serum chemistry parameters, and histological evaluation of tissues from throughout the body were analyzed. Both experiments indicated that there was no significant difference in the examined parameters between the Ad-REIC-treated group and the control (PBS- or Ad-LacZ-treated) group. In the in vitro analysis using PC3 cells, a significant apoptotic effect was observed after Ad-hREIC treatment. Confirming this observation, the robust anti-tumor efficacy of Ad-hREIC was demonstrated in the in vivo subcutaneous prostate cancer model. Based on the results of these preclinical experiments, we consider the adenovirus-mediated REIC/Dkk-3 in situ gene therapy to be safe and useful for the clinical treatment of prostate cancer.
Keywords
REIC
Dickkopf-3
gene therapy
prostate cancer
preclinical study
Amo Type
Original Article
Published Date
2012-02
Publication Title
Acta Medica Okayama
Volume
volume66
Issue
issue1
Publisher
Okayama University Medical School
Start Page
7
End Page
16
ISSN
0386-300X
NCID
AA00508441
Content Type
Journal Article
language
英語
Copyright Holders
CopyrightⒸ 2012 by Okayama University Medical School
File Version
publisher
Refereed
True
PubMed ID
Web of Sience KeyUT