Gene Therapy of HSV-TK Transferred by the EBV based Expression Vector on Experimental Hepatocellular Carcinoma

Hepatocellular carcinoma(HCC) is a commonmalignancy with increasing incidence and poor prog-nosis.Up to now,a wide array of gene therapy sys-tems for the tumor have been investigated.Herpessimplex virus thymidine kinase (HSV- TK ) genetransfer followed by gancinovir(GCV) administra-tion is one of the most well- established suicide genesystems.HSV- TK converts the protoxic nucleosideanalogue GCV into a highly toxic,phosphorylatedGCV that acts as a chain terminator of DNA synthe-sis an…

Gene therapy of HSV-TK transferred by the EBV based expression vector on experimental hepatocellular carcinoma

Summary To study the therapeutic effects of herpes simplex virus thymidine kinase (HSV-TK) gene transferred by the EBV-based expression vector (pDR2) on experimental hepatocellular carcinoma, pDR2-TK gene was delivered into human hepatocellular carcinoma cell line SMMC-7721 by using liposome-mediated transfection technique, and then gene expression was detected by RT-PCR, and the killing effects were examined through MTT method. In the nude mice hepatoma model, the antitumor effects of pDR2-TK/GCV system was evaluated in terms of tumor growth. MTT results showed that the pDR2-TK/GCV had cytotoxic effect and about 70% SMMC-7721 cells were killed when GCV was at 1000 μmol/L.In vivo experiment showed that the tumor size in nude mice with transferred pDR2-TK gene was significantly smaller than that in control group (P< 0. 01). On the 10th day the tumor in 3 mice (60 %) disappeared completely after GCV treatment. It is concluded that the pDR2-TK/GCV system has marked killing effects on the experimental hepatocellular carcinoma.