title: Preclinical safety and efficacy of in situ REIC/Dkk-3 gene therapy for prostate cancer.
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.
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kawauchi
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Haruki
authors.initials: H
authors.lastname: Kaku
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Kasumi
authors.initials: K
authors.lastname: Sasaki
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ochiai
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D018925:Chemokines; D015316:Genetic Therapy / Q000009:adverse effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins