Adenovirus vector-mediated herpes simplex virus-thymidine kinase gene/ganciclovir system exhibits anti-tumor effects in an orthotopic hepatocellular carcinoma model

Abstract

Adenovirus vector-mediated herpes simplex virus-thymidine kinase/ganciclovir (ADV.tk/GCV) system is a promising approach for cancer gene therapy. This study aimed to investigate the anti-tumor efficacy and the underlying mechanisms of ADV.tk/GCV system in orthotopic hepatocellular carcinoma (HCC) model. A total of 132 female nude mice orthotopic HCC models were established and tumors were directly injected with ADV.tk (5.0 x 10(6) vector particles/kg) or saline solution, 24 h later the animals were intraperitoneally administrated by ganciclovir (30 mg/kg) or saline solution for 7 consecutive days. We observed that ADV.tk/GCV resulted in a significant regression of tumor growth and a significant prolongation of survival of the mice. At each given time point, the percentages of cleaved caspae-3, caspase-9 and TUNEL positive cells were significantly higher in the ADV.tk + GCV group than saline group (P < 0.005), while CD31 and VEGF staining were significantly less in ADV.tk + GCV group than in saline group (P < 0.005). In summary, ADV.tk/GCV system exhibits dramatic anti-tumor effects in orthotopic hepatocellular carcinoma model by promoting apoptosis and inhibiting angiogenesis, and is a promising treatment strategy for hepatic carcinoma.