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Background: This study aimed to develop a novel tumor-specific promoter gene linking sodium iodide symporter (NIS) gene to specifically target hepatocellular carcinoma in a mouse tumor model., Materials and Methods: A tumor-specific chimeric promoter for alpha-fetoprotein gene (AFP) was combined with hepatitis B virus (HBV) enhancer II to investigate radioiodine uptake in vitro and in vivo in hepatoma (HepG2) and nonhepatoma (ARO) cell lines after transfer of hNIS gene. A lentiviral vector carrying the hNIS gene was employed in vitro and in vivo. Radionuclide imaging was acquired for 30 min at 60 min after administration of 1241 to monitor hNIS gene expression in vivo using microPET., Results: The highest radioiodide uptake of ARO and HepG2 clones which stably expressed hNIS gene were 87- and 208-fold higher than that of parental cells, respectively. After infection of lentivirus, hNIS gene controlled by cytomegavirus (CMV) promoter was expressed in both ARO and HepG2 cells, and hNIS gene induction by EIIAPA promoter was higher than by CMV promoter in HepG2 cells but not in ARO cells. A similar result was observed in vivo, hNIS controlled by CMV promoter was highly expressed in both HepG2 and ARO tumors. The HepG2 tumor multi-infected with LV-EIIAPA-hNIS virus specifically, but the ARO tumor did not activate the EIIAPA promoter and further express the hNIS protein., Conclusion: Transduction of the hNIS gene controlled by the novel EIIAPA chimeric promoter successfully induces iodide transport in hepatoma.

Background: Most undifferentiated and anaplastic thyroid carcinomas are not sensitive to 131I therapy due to their lost ability for iodide accumulation. This study aims to restore the iodide uptake by transferring and expressing human sodium iodide symporter (hNIS) in these cancer cells for 131I gene therapy., Materials and Methods: hNIS cDNA expression vector was transfected into wild-type anaplastic thyroid cancer cells (ARO-W) which do not concentrate iodide. Stable trasfected cells were isolated (ARO-S) and analyzed by RT-PCR, radioiodide uptake and immunocyto-chemistry staining. 131I imaging and treatment were performed on mice bearing ARO-W and ARO-S xenograft tumors and tumor volume was recorded., Results: The ARO-S cells showed clear hNIS expression on the cell membrane and accumulated 87-fold and 4.4-fold radioiodide of that of wild-type cells in vitro and in vivo, respectively. Radioiodide uptake was dependent on cell number and reached a maximum level at 20 minutes in vitro. The half life of radioiodide efflux was 12 minutes and 12 hours in vitro and in vivo, respectively. Administration of a therapeutic dose of 131I into mice bearing ARO-S tumors effectively inhibited tumor growth as compared to control mice., Conclusion: Our results suggest the potential of hNIS-mediated 131I gene therapy on anaplastic thyroid cancer cells.

Background: To specifically target malignant cells, cancer gene therapy needs to combine highly selective gene delivery with highly specific gene expression. In this study, hepatitis B virus (HBV) enhancer II was combined with alpha-fetoprotein (AFP) promoter which selectively controls the Cre/loxP system in hepatoma., Materials and Methods: pE4luc, pE4Tk, EIIAPA-Cre and E4CMV-STOP-Tk constructs and AFP promoter combined with HBV enhancer were constructed and transfected into HepG2, HeLa and NIH-3T3 cell lines., Results: The E4 enhancer showed the highest luciferase gene expression at a dose range of 5 approximately 7 Gy after 60 hours irradiation. The EIIAPA chimeric promoter which controls the Cre/loxP system provided high specificity only to the hepatoma cells. In addition, the E4 response to radiation encoded more Herpes simplex virus thymidine kinase (HSV1-Tk) protein and killed more tumor cells., Conclusion: The chimeric EIIAPA promoter can precisely control the Cre/loxP switch and the radiation effect on the EIIAPA-Cre and E4CMV-STOP-Tk system shows promising results in terms of cell survival of hepatocellular carcinoma (HCC).