The glial fibrillary acidic protein promoter directs sodium/iodide symporter gene expression for radioiodine therapy of malignant glioma

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Publisher： Spandidos Publications

ISSN： 1792-1074

Source： Oncology Letters, Vol.5, Iss.2, 2013-01, pp. : 669-674

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Abstract

Radioiodine is a routine therapy for differentiated thyroid cancers. Nonthyroid cancers may be treated with radioiodine following transfection with the human sodium/iodide symporter (hNIS) gene. The glial fibrillary acidic protein (GFAP) promoter is an effective tumorspecific promoter for gene expression and thus may be useful in targeted gene therapy of malignant glioma. The present study used GFAP promotermodulated expression of the hNIS gene in an experimental model of radioiodinebased treatment for malignant glioma. Cells were transfected using a recombination adenovirus and evaluated in cells by studying the transfected transgene expression through western blot analysis, 125I uptake and efflux, clonogenicity following 131I treatment and radioiodine therapy using a U87 xenograft nude mouse model. Following transfection with the hNIS gene, the cells showed 9570fold higher 125I uptake compared with the control cells transfected with Adcytomegalovirus (CMV)enhanced green fluorescent protein (EGFP). The western blotting revealed bands of ~70, 49 and 43 kDa, consistent with the hNIS, GFAP and βactin proteins. The clonogenic assay indicated that, following exposure to 500 µCi of 131Iiodide for 12 h, >90% of cells transfected with the hNIS gene were killed. AdGFAPhNIS-transfected and 2 mCi 131I-injected U87 xenograft nude mice survived the longest of the three groups. The hNISexpressing tumor tissue accumulated 99mTcO4 rapidly within 30 min of it being intraperitoneally injected. The experiments demonstrated that effective 131I therapy was achieved in the malignant glioma cell lines following the induction of tumorspecific iodide uptake activity by GFAP promoterdirected hNIS gene expression in vitro and in vivo. 131I therapy retarded AdGFAPhNIS transfectedtumor growth following injection with 131I in U87 xenograftbearing nude mice.