Combined radionuclide–chemotherapy and in vivo imaging of hepatocellular carcinoma cells after transfection of a triple-gene construct, NIS, HSV1-sr39tk, and EGFP

• Published in: Cancer letters 2010-04, Vol.290 (1), p.129-138
• Main Authors: Lee, You La, Lee, Yong Jin, Ahn, Sohn Joo, Choi, Tae Hyun, Moon, Byung Seok, Cheon, Gi Jeong, Lee, Sang-Woo, Ahn, Byeong-Cheol, Ha, Jeoung-Hee, Lee, Jaetae
• Format: Article
• Language: English
• Subjects: Animals; Cancer therapies; Carcinoma, Hepatocellular - diagnostic imaging; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - therapy; Cell Line, Tumor; Cell survival; EGFP; Enzymes; Gene expression; Gene therapy; Genes, Reporter; Genetic Therapy - methods; Genetic Vectors; Green Fluorescent Proteins - genetics; Hematology, Oncology and Palliative Medicine; Human sodium iodide symporter; Humans; I-124; Iodine Radioisotopes - pharmacology; Kinases; Liver cancer; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - genetics; Liver Neoplasms - therapy; Male; Mice; Mice, Nude; Mutant herpes-simplex virus type1 sr39 thymidine kinase; Positron-Emission Tomography; Prodrugs - pharmacology; Radiopharmaceuticals - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Simplexvirus - genetics; Symporters - genetics; Thymidine Kinase - genetics; Transfection; Triple-reporter gene; Tumors; Xenograft Model Antitumor Assays
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2009.09.004

Abstract The sodium iodine symporter (NIS) or mutant Herpes-simplex virus type1 sr39 thymidine kinase (HSV1-sr39tk) gene is used for in vivo imaging and cancer therapy. Transfection of both NIS and HSV1-sr39tk genes to hepatocellular carcinoma cells (Huh-7/NTG) could enhance intracellular accumulation of therapeutic radionuclides and guanosine nucleoside analogue prodrugs to produce better outcomes than single gene therapy. Non-invasive imaging with I-124, F-18 FHBG and combination therapy with I-131 and GCV were performed in hepatocellular carcinoma cells transfected with NIS, HSV1-sr39tk and GFP. Our results show that: (1) all three genes are stably expressed in Huh-7/NTG cells, (2) I-125 and H3-PCV uptake were markedly increased in the Huh-7/NTG cells in vitro , (3) cellular survival and tumor growth of Huh-7/NTG was inhibited by I-131 or GCV both in vitro and in vivo , and was much prominent with combination therapy, (4) in vivo imaging with I-124 and F-18 FHBG revealed increased uptake in the Huh-7/NTG tumor. Our results demonstrated the potential of combination gene therapy using NIS and HSV1-sr39tk followed by radioiodine treatment and chemotherapy in human hepatocellular carcinoma cells.