Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model

被引：13

作者：

Ahn, S. J. ^{[1
]}

Jeon, Y. H. ^{[1
]}

Lee, Y. J. ^{[1
]}

Lee, Y. L. ^{[1
]}

Lee, S-W ^{[1
]}

Ahn, B-C ^{[1
]}

Ha, J-H ^{[2
]}

Lee, J. ^{[1
]}

机构：

[1] Kyungpook Natl Univ, Dept Nucl Med, Sch Med, Taegu, South Korea

[2] Kyungpook Natl Univ, Dept Pharmacol, Sch Med, Taegu, South Korea

来源：

CANCER GENE THERAPY | 2010年 / 17卷 / 07期

基金：

新加坡国家研究基金会;

关键词：

MDR1; shRNA; hNIS; Radioiodine gene therapy; imaging; SODIUM-IODIDE SYMPORTER; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; PROSPECTS; PROGRESS; VECTORS; VIRUS; CELLS;

D O I：

10.1038/cgt.2010.3

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS) radioiodine gene therapy in a mouse colon xenograft model. In vitro uptake of Tc-99m sestamibi was increased approximately two-fold in cells infected with an adenovirus vector that expressed MDR1 shRNA (Ad-shMDR1) and I-125 uptake was 25-fold higher in cells infected with an adenovirus vector that expressed human NIS (Ad-hNIS) as compared with control cells. As compared with doxorubicin or I-131 treatment alone, the combination of doxorubicin and I-131 resulted in enhanced cytotoxicity for both Ad-shMDR1- and Ad-hNIS-infected cells, but not for control cells. In vivo uptake of Tc-99m sestamibi and Tc-99m pertechnetate was twofold and 10-fold higher for Ad-shMDR1 and Ad-hNIS-infected tumors as compared with tumors infected with a control adenovirus construct that expressed beta-galactrosidase (Ad-LacZ), respectively. In mice treated with either doxorubicin or I-131 alone, there was a slight delay in tumor growth as compared to mice treated with Ad-LacZ. However, combination therapy with doxorubicin and I-131 induced further significant inhibition of tumor growth as compared with mice treated with Ad-LacZ. We have shown successful therapeutic efficacy of combined MDR shRNA and hNIS radioiodine gene therapy using an adenoviral vector system in a mouse colon cancer model. Adenovirus-mediated cancer gene therapy using MDR1 shRNA and hNIS would be a useful tool for the treatment of cancer cells expressing multi-drug resistant genes. Cancer Gene Therapy (2010) 17, 492-500; doi:10.1038/cgt.2010.3; published online 26 February 2010

引用

页码：492 / 500

页数：9

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