Brief Article
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World J Gastroenterol. Nov 14, 2010; 16(42): 5367-5374
Published online Nov 14, 2010. doi: 10.3748/wjg.v16.i42.5367
Baculovirus vector-mediated transfer of NIS gene into colon tumor cells for radionuclide therapy
Hong-Yan Yin, Xiang Zhou, Hai-Fei Wu, Biao Li, Yi-Fan Zhang
Hong-Yan Yin, Xiang Zhou, Hai-Fei Wu, Biao Li, Yi-Fan Zhang, Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Author contributions: Yin HY and Zhou X performed the majority of experiments; Wu HF performed parts of the experiments; Li B designed parts of the studies; Zhang YF designed the majority of the studies and wrote the manuscript.
Supported by Grants from the National Natural Science Foundation of China, No. 30570525; and the Shanghai Leading Academic Discipline Project, No. S30203
Correspondence to: Dr. Yi-Fan Zhang, Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Rui Jin 2nd Road, Shanghai 200025, China. zhangyifan1992@yahoo.com.cn
Telephone: +86-21-64314813 Fax: +86-21-64333548
Received: June 30, 2010
Revised: August 2, 2010
Accepted: August 9, 2010
Published online: November 14, 2010
Abstract

AIM: To investigate the feasibility of radionuclide therapy of colon tumor cells by baculovirus vector-mediated transfer of the sodium/iodide symporter (NIS) gene.

METHODS: A recombinant baculovirus plasmid carrying the NIS gene was constructed, and the viruses (Bac-NIS) were prepared using the Bac-to-Bac system. The infection efficiency in the colon cancer cell line SW1116 of a green fluorescent protein (GFP) expressing baculovirus (Bac-GFP) at different multiplicities of infection (MOI) with various concentrations of sodium butyrate was determined by flow cytometry. An in vitro cytotoxicity assay was also conducted after infection of SW1116 cells with Bac-NIS. Iodine uptake of Bac-NIS infected SW1116 cells and inhibition of this uptake by sodium perchlorate was examined, and the effect of Bac-NIS-mediated 131I in killing tumor cells was evaluated by cell colony formation tests.

RESULTS: Infection and transgene expression in SW1116 with Bac-GFP were significantly enhanced by sodium butyrate, as up to 72% of SW1116 cells were infected with the virus at MOI of 400 and sodium butyrate at 0.5 mmol/L. No obvious cytotoxicity was observed under these conditions. Infection of SW1116 with Bac-NIS allowed uptake of 131I in these tumor cells, which could be inhibited by sodium perchlorate. The viability of SW1116 cells infected with Bac-NIS was significantly lower than with Bac-GFP, suggesting that NIS gene-mediated 131I uptake could specifically kill tumor cells.

CONCLUSION: Baculovirus vector-mediated NIS gene therapy is a potential approach for treatment of colon cancer.

Keywords: Colon cancer; Baculovirus; Sodium iodide symporter; Radionuclide therapy; Iodine radioisotopes