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ID 53015
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Author
Uchida, Daisuke
Nagahara, Teruya
Kataoka, Junro
Horiguchi, Shigeru
Nasu, Yasutomo
Abstract
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.
Keywords
apoptosis
autophagy
dickkopf-related protein
gene therapy
mTOR pathway
Note
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
Published Date
2014-05
Publication Title
Journal of Gastroenterology and Hepatology
Volume
volume29
Issue
issue5
Start Page
973
End Page
983
ISSN
0815-9319
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52971
language
英語
Copyright Holders
© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
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Refereed
True
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