Study On Radiochemotherapy Of Hepatocarcinoma Va HNIS Gene And HSV-TK Gene

BACKGROUND & PURPOSE: Herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) has been wildly used as a traditional gene therapy modality, and the sodium/iodide symporter gene (NIS) has been found to be a novel therapeutic gene. However, the therapeutic effects of both genes need to be enhanced. The purpose of this study was to investigate the feasibility of radiochemotherapy for hepatocarcinoma via co-expression of human sodium iodide symporter gene and herpes simplex virus thymidine kinase 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 fluorescence imaging, RT-PCR, MTT assay, and iodide uptake. The therapeutic effects were further assessed by clonogenic assay.RESULTS: Gene expression was demonstrated by fluorescence imaging, RT-PCR, MTT assay, and radioiodide uptake. Stably transfected cells concentrated 125I up to 76-fold higher than the wild-type cells within 20 minutes,then the efflux happened with a T1/2eff 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 131I was revealed by both clonogenic assay and MTT assay. The survival rate of HepG2/NTG cells decreased to 49.69%±2.54 %, 43.38%±2.80%, and 8.55%±1.22% after exposure to 131I, GCV and combined therapy, respectively.CONCLUSION: Radiochemotherapy for hepatocarcinoma via co-expression of hNIS gene and HSV-TK gene is feasible. In vivo study is needed to verify these findings.