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ID 53015
フルテキストURL
著者
Uchida, Daisuke Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Shiraha, Hidenori Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Kato, Hironari Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci 科研費研究者番号
Nagahara, Teruya Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Iwamuro, Masaya Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Kataoka, Junro Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Horiguchi, Shigeru Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Watanabe, Masami Okayama Univ, Dept Urol, Grad Sch Med Dent & Pharmaceut Sci
Takaki, Akinobu Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci 科研費研究者番号
Nouso, Kazuhiro Okayama Univ, Dept Mol Hepatol, Grad Sch Med Dent & Pharmaceut Sci
Nasu, Yasutomo Okayama Univ, Dept Urol, Grad Sch Med Dent & Pharmaceut Sci
Yagi, Takahito Okayama Univ, Dept Gastroenterol Surg Transplant & Surg Oncol, Grad Sch Med Dent & Pharmaceut Sci
Kumon, Hiromi Okayama Univ, Dept Urol, Grad Sch Med Dent & Pharmaceut Sci
Yamamoto, Kazuhide Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
抄録
Background and AimThe reduced expression in immortalized cells REIC/the dickkopf 3 (Dkk-3) gene, tumor suppressor gene, is downregulated in various malignant tumors. In a prostate cancer study, an adenovirus vector carrying the REIC/Dkk-3 gene (Ad-REIC) induces apoptosis. In the current study, we examined the effects of REIC/Dkk-3 gene therapy in pancreatic cancer. MethodsREIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry in the pancreatic cancer cell lines (ASPC1, MIAPaCa2, Panc1, BxPC3, SUIT-2, KLM1, and T3M4) and pancreatic cancer tissues. The Ad-REIC agent was used to investigate the apoptotic effect in vitro and antitumor effects in vivo. We also assessed the therapeutic effects of Ad-REIC therapy with gemcitabine. ResultsThe REIC/Dkk-3 expression was lost in the pancreatic cancer cell lines and decreased in pancreatic cancer tissues. Ad-REIC induced apoptosis and inhibited cell growth in the ASPC1 and MIAPaCa2 lines in vitro, and Ad-REIC inhibited tumor growth in the mouse xenograft model using ASPC1 cells. The antitumor effect was further enhanced in combination with gemcitabine. This synergistic effect may be caused by the suppression of autophagy via the enhancement of mammalian target of rapamycin signaling. ConclusionsAd-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.
キーワード
apoptosis
autophagy
dickkopf-related protein
gene therapy
mTOR pathway
備考
This is the accepted version of the following article: FULLCITE, which has been published in final form at http://dx.doi.org/10.1111/jgh.12501
発行日
2014-05
出版物タイトル
Journal of Gastroenterology and Hepatology
29巻
5号
開始ページ
973
終了ページ
983
ISSN
0815-9319
資料タイプ
学術雑誌論文
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/52971
言語
English
著作権者
© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT