title: 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.
authors: Ruidong
authors: R
authors: Zhu
authors: Dexi
authors: D
authors: Chen
authors: Dongdong
authors: D
authors: Lin
authors: Fudong
authors: F
authors: Lu
authors: Jiming
authors: J
authors: Yin
authors: Ning
authors: N
authors: Li
mesh_terms: D020533:Angiogenesis Inhibitors; D000818:Animals; D024201:Bystander Effect; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; D013937:Thymidine Kinase; D015774:Ganciclovir