JaLCDOI 10.18926/AMO/54982
フルテキストURL 71_2_135.pdf
著者 Mori, Akihiro| Watanabe, Masami| Sadahira, Takuya| Kobayashi, Yasuyuki| Ariyoshi, Yuichi| Ueki, Hideo| Wada, Koichiro| Ochiai, Kazuhiko| Li, Shun-Ai| Nasu, Yasutomo|
抄録 The cluster of differentiation 147 (CD147), also known as EMMPRIN, is a key molecule that promotes cancer progression. We previously developed an adenoviral vector encoding a tumor suppressor REIC/Dkk-3 gene (Ad-REIC) for cancer gene therapy. The therapeutic effects are based on suppressing the growth of cancer cells, but, the underlying molecular mechanism has not been fully clarified. To elucidate this mechanism, we investigated the effects of Ad-REIC on the expression of CD147 in LNCaP prostate cancer cells. Western blotting revealed that the expression of CD147 was significantly suppressed by Ad-REIC. Ad-REIC also suppressed the cell growth of LNCaP cells. Since other researchers have demonstrated that phosphorylated mitogen-activated protein kinases (MAPKs) and c-Myc protein positively regulate the expression of CD147, we investigated the correlation between the CD147 level and the activation of MAPK and c-Myc expression. Unexpectedly, no positive correlation was observed between CD147 and its possible regulators, suggesting that another signaling pathway was involved in the downregulation of CD147. This is the first study to show the downregulation of CD147 by Ad-REIC in prostate cancer cells. At least some of the therapeutic effects of Ad-REIC may be due to the downregulation of the cancer-progression factor, CD147.
キーワード prostate cancer REIC/Dkk-3 CD147 cell growth p38 MAP kinase
Amo Type Original Article
発行日 2017-04
出版物タイトル Acta Medica Okayama
71巻
2号
出版者 Okayama University Medical School
開始ページ 135
終了ページ 142
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
著作権者 CopyrightⒸ 2017 by Okayama University Medical School
論文のバージョン publisher
査読 有り
PubMed ID 28420895
著者 Sakaguchi, Masakiyo| Kataoka, Ken| Abarzua, Fernando| Tanimoto, Ryuta| Watanabe, Masami| Murata, Hitoshi| Than, Swe Swe| Kurose, Kaoru| Kashiwakura, Yuji| Ochiai, Kazuhiko| Nasu, Yasutomo| Kumon, Hiromi| Huh, Nam-ho|
発行日 2009-05-22
出版物タイトル The Journal of Biological Chemistry
284巻
21号
資料タイプ 学術雑誌論文
JaLCDOI 10.18926/AMO/48076
フルテキストURL 66_1_7.pdf
著者 Kawauchi, Keiichiro| Watanabe, Masami| Kaku, Haruki| Huang, Peng| Sasaki, Kasumi| Sakaguchi, Masakiyo| Ochiai, Kazuhiko| Huh, Nam-ho| Nasu, Yasutomo| Kumon, Hiromi|
抄録 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.
キーワード REIC Dickkopf-3 gene therapy prostate cancer preclinical study
Amo Type Original Article
発行日 2012-02
出版物タイトル Acta Medica Okayama
66巻
1号
出版者 Okayama University Medical School
開始ページ 7
終了ページ 16
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
著作権者 CopyrightⒸ 2012 by Okayama University Medical School
論文のバージョン publisher
査読 有り
PubMed ID 22358134
Web of Sience KeyUT 000300800700002
著者 Ochiai, Kazuhiko| Watanabe, Masami| Ueki, Hideo| Huang, Peng| Fujii, Yasuyuki| Nasu, Yasutomo| Noguchi, Hirofumi| Hirata, Takeshi| Sakaguchi, Masakiyo| Huh, Nam-ho| Kashiwakura, Yuji| Kaku, Haruki| Kumon, Hiromi|
発行日 2011-08-26
出版物タイトル Biochemical and Biophysical Research Communications
412巻
2号
資料タイプ 学術雑誌論文