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
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Kato, Hironari
Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
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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
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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
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Takaki, Akinobu
Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci
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Nouso, Kazuhiro
Okayama Univ, Dept Mol Hepatol, Grad Sch Med Dent & Pharmaceut Sci
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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
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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.
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キーワード | apoptosis
autophagy
dickkopf-related protein
gene therapy
mTOR pathway
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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
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発行日 | 2014-05
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出版物タイトル |
Journal of Gastroenterology and Hepatology
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巻 | 29巻
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号 | 5号
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開始ページ | 973
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終了ページ | 983
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ISSN | 0815-9319
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資料タイプ |
学術雑誌論文
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/52971
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言語 |
英語
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著作権者 | © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |