title: Radiochemotherapy of hepatocarcinoma via lentivirus-mediated transfer of human sodium iodide symporter gene and herpes simplex virus thymidine kinase gene.
abstract: Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system has been widely used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. Since the therapeutic effects of radioiodine therapy or prodrug chemotherapy on cancers following NIS or HSV-TK gene transfer need to be enhanced, this study was designed to investigate the feasibility of radiochemotherapy for hepatocarcinoma via coexpression of NIS gene and HSV-TK gene.
  
  
  METHODS
  HepG2 cells were stably transfected with NIS, TK and GFP gene via recombinant lentiviral vector and named HepG2/NTG. Gene expression was examined by reverse transcriptase polymerase chain reaction, fluorescence imaging and iodide uptake. The therapeutic effects were assessed by MTT assay and clonogenic assay.
  
  
  RESULTS
  HepG2/NTG cells concentrated (125)I(-) up to 76-fold higher than the wild-type cells within 20 min, and the efflux happened with a T(1/2eff) of less than 10 min. The iodide uptake in HepG2/NTG cells was specifically inhibited by sodium perchlorate. Dose-dependent toxicity to HepG2/NTG cells by either GCV or (131)I was revealed by clonogenic assay and MTT assay, respectively. The survival rate of HepG2/NTG cells decreased to 49.7%±2.5%, 43.4%±2.8% and 8.6%±1.2% after exposure to (131)I, GCV and combined therapy, respectively.
  
  
  CONCLUSIONS
  We demonstrate that radiochemotherapy of hepatocarcinoma via lentiviral-mediated coexpression of NIS gene and HSV-TK gene leads to stronger killing effect than single treatment, and in vivo studies are needed to verify these findings.
authors: Department of Nuclear Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, PR China. libochen888@hotmail.com
authors: Libo
authors: L
authors: Chen
authors: Guoying
authors: G
authors: Guo
authors: Tianjing
authors: T
authors: Liu
authors: Lihe
authors: L
authors: Guo
authors: Ruisen
authors: R
authors: Zhu
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D015774:Ganciclovir / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D007454:Iodides / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*; D018139:Simplexvirus / Q000235:genetics*; D027981:Symporters / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*; D014162:Transfection; D000099209:Sodium-Iodide Symporters
chemical_list: D015774:Ganciclovir; D007454:Iodides; D027981:Symporters; D013937:Thymidine Kinase; D000099209:Sodium-Iodide Symporters