Radioiodine gene therapy of hepatocellular carcinoma targeted human alpha fetoprotein.
Cancer Biother Radiopharm
; 23(5): 551-60, 2008 Oct.
Article
en En
| MEDLINE
| ID: mdl-18986218
ABSTRACT
INTRODUCTION:
We conducted a molecular imaging and gene therapy method in alpha-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) by tumor-specific expression of the human sodium/iodide symporter (hNIS) using an AFP promoter.METHODS:
The tumor-specific expression of hNIS gene by the AFP enhancer/promoter was constructed as pcDNA3-AFP/hNIS. The pcDNA3-AFP/hNIS was stably transfected to human HCC (Huh-7/AN) and rat glioma cells (C6/AN). Functional hNIS expression was confirmed by radioiodine uptake. The mRNA and protein-expression level of hNIS were measured. Biodistribution of 131I was evaluated, and scintigraphic images of 99mTc were obtained in xenografted mice. A clonogenic assay was performed by 131I. And, the in vivo therapeutic effect of 131I was evaluated in xenografted mice.RESULTS:
In Huh-7/AN cells, iodine was highly accumulated and completely blocked by perchlorate. The protein and mRNA expression levels were correlated with iodine uptake. Radioiodine uptake in Huh-7/AN tumors was higher than those of control tumors and clearly visualized. The survival rate was significantly decreased in Huh-7/AN cells by 131I. Moreover, a growth of Huh-7/AN tumors was inhibited by 131I in mice.CONCLUSIONS:
AFP-producing hepatoma can be targeted and treated with radionuclides and hNIS, using AFP enhancer/promoter. This targeted hNIS gene therapy and molecular imaging have the potential to be used in the management of AFP-producing HCC.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Terapia Genética
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Alfa-Fetoproteínas
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Carcinoma Hepatocelular
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Radioisótopos de Yodo
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Neoplasias Hepáticas
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cancer Biother Radiopharm
Asunto de la revista:
FARMACIA
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FARMACOLOGIA
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NEOPLASIAS
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TERAPEUTICA
Año:
2008
Tipo del documento:
Article