3 votes

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

Sohn Joo Ahn¹, Yong Hyun Jeon¹, Yong Jin Lee¹, You La Lee¹, Sang-Woo Lee¹, Byeong-Cheol Ahn¹, Jeoung-Hee Ha² & Jaetae Lee¹

Correspondence: (Login to view email address)

1. Department of Nuclear Medicine, School of Medicine, Kyungpook National University
2. Department of Pharmacology, School of Medicine, Kyungpook National University

PDF (1 MB)

Document Type:

Manuscript

Date:

Received 02 June 2009 13:12 UTC; Posted 02 June 2009

Subjects:

Cancer

Tags:

• hNIS
• radioiodine
• small hairpin RNA
• colon cancer
• gene therapy
• combination therapy
• MDR1
• shRNA
• tumors
• adenovirus
• doxorubicin

Abstract:

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-shMDR) and I-125 uptake was 25-fold higher in cells infected with an adenovirus vector that expressed human NIS (Ad-hNIS) as compared to 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-shMDR and Ad-hNIS infected cells but not for control cells. In vivo uptake of Tc-99m sestamibi and Tc-99m pertechnetate was two-fold and 10-fold higher for Ad-shMDR and Ad-hNIS-infected tumors as compared to tumors infected with a control adenovirus construct that expressed β-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 demonstrated 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.

Discussion

Votes:

3 votes

(Login to vote)

Comments:

0 comments

(Login to post a comment)

Share:

(Login to share with a colleague)

Additional information

License:

This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Ahn, Sohn Joo, Jeon, Yong Hyun, Lee, Yong Jin, Lee, You La, Lee, Sang-Woo, Ahn, Byeong-Cheol, Ha, Jeoung-Hee, and Lee, Jaetae. 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. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.3307.1> (2009)

Version info:

Other versions of this document in Nature Precedings

None.

Other versions of this document elsewhere on the web

None known.

Submit a new version link