Targeting gene-virus-mediated manganese superoxide dismutase effectively suppresses tumor growth in hepatocellular carcinoma in vitro and in vivo.

Although the treatment methods for hepatocellular carcinoma (HCC) have made a great progress on patient survival rate and life quality, the HCC recurrence still is very high. To explore the novel effective anticancer strategies for HCC, the Cancer Targeting Gene-Viro-Therapy (CTGVT) strategy was applied through oncolytic virus-delivery antitumor gene. In this article, the dual-regulated oncolytic adenovirus Ad-AFP-E1A-E1B(Δ55kDa)-Mn-SOD (briefly named AD55-Mn-SOD) was constructed using a liver cancer-specific α-fetoprotein (AFP) promoter to control replication-essential E1A gene and deliver the novel tumor suppression gene Manganese superoxide dismutase (Mn-SOD). The results indicated that the constructed AD55-Mn-SOD exerted tumor-specific features, and induced dramatic cytotoxicity in HCC cells in vitro and suppress the HCC xenografted growth in nude mice. Moreover, the anticancer mechanism of AD55-Mn-SOD is due to the activation of caspase apoptotic pathway. These data suggested that AD55-Mn-SOD could become a potential anticancer agent for liver cancer.