Combined radionuclide-chemotherapy and in vivo imaging of hepatocellular carcinoma cells after transfection of a triple-gene construct, NIS, HSV1-sr39tk, and EGFP.
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.
Lee
You La
YL
Department of Nuclear Medicine and Pharmacology, Kyungpook National University, Daegu, Republic of Korea.
Lee
Yong Jin
YJ
Ahn
Sohn Joo
SJ
Choi
Tae Hyun
TH
Moon
Byung Seok
BS
Cheon
Gi Jeong
GJ
Lee
Sang-Woo
SW
Ahn
Byeong-Cheol
BC
Ha
Jeoung-Hee
JH
Lee
Jaetae
J
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D011355:Prodrugs / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000235:genetics; D027981:Symporters / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
D049452:Green Fluorescent Proteins; D007457:Iodine Radioisotopes; D011355:Prodrugs; D019275:Radiopharmaceuticals; D027981:Symporters; D013937:Thymidine Kinase; D000099209:Sodium-Iodide Symporters; C485184:enhanced green fluorescent protein