MISC

2009年1月

REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer

CANCER GENE THERAPY
  • K. Kawasaki
  • M. Watanabe
  • M. Sakaguchi
  • Y. Ogasawara
  • K. Ochiai
  • Y. Nasu
  • H. Doihara
  • Y. Kashiwakura
  • N-h Huh
  • H. Kumon
  • H. Date
  • 全て表示

16
1
開始ページ
65
終了ページ
72
記述言語
英語
掲載種別
DOI
10.1038/cgt.2008.58
出版者・発行元
NATURE PUBLISHING GROUP

The overexpression of reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in human prostatic and testicular cancer cells. The aim of this study is to examine the potential of REIC/Dkk-3 as a therapeutic target against breast cancer. First, the in vitro apoptotic effect of Ad-REIC treatment was investigated in breast cancer cell lines and the adenovirus-mediated overexpression of REIC/Dkk-3 was thus found to lead to apoptotic cell death in a c-Jun-NH(2)-kinase (JNK) phosphorylaion-dependent manner. Moreover, an in vivo apoptotic effect and MCF/Wt tumor growth inhibition were observed in the mouse model after intratumoral Ad-REIC injection. As multidrug resistance (MDR) is a major problem in the chemotherapy of progressive breast cancer, the in vitro effects of Ad-REIC treatment were investigated in terms of the sensitivity of multidrug-resistant MCF7/ADR cells to doxorubicin and of the P-glycoprotein expression. Ad-REIC treatment in MCF7/ADR cells also downregulated P-glycoprotein expresssion through JNK activation, and sensitized its drug resistance against doxorubicin. Therefore, not only apoptosis induction but also the reversal of anticancer drug resistance was achieved using Ad-REIC. We suggest that REIC/Dkk-3 is a novel target for breast cancer treatment and that Ad-REIC might be an attractive agent against drug-resistant cancer in combination with conventional antineoplastic agents.

リンク情報
DOI
https://doi.org/10.1038/cgt.2008.58
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000261703100007&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/cgt.2008.58
  • ISSN : 0929-1903
  • Web of Science ID : WOS:000261703100007

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