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

被引：0
作者：
K Kawasaki
M Watanabe
M Sakaguchi
Y Ogasawara
K Ochiai
Y Nasu
H Doihara
Y Kashiwakura
N-h Huh
H Kumon
H Date
机构：
[1] Graduate School of Medicine,Department of Cancer and Thoracic Surgery
[2] Dentistry and Pharmaceutical Sciences,Department of Urology
[3] Okayama University,Department of Cell Biology
[4] Graduate School of Medicine,undefined
[5] Dentistry and Pharmaceutical Sciences,undefined
[6] Okayama University,undefined
[7] Innovation Center Okayama for Nanobio-Targeted Therapy,undefined
[8] Graduate School of Medicine,undefined
[9] Dentistry and Pharmaceutical Sciences,undefined
[10] Okayama University,undefined
[11] Graduate School of Medicine,undefined
[12] Dentistry and Pharmaceutical Sciences,undefined
[13] Okayama University,undefined
来源：
Cancer Gene Therapy | 2009年 / 16卷
关键词：
REIC/Dkk-3; breast cancer; apoptosis; P-glycoprotein;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
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-NH2-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.
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页码：65 / 72
页数：7
相关论文
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