title: Targeting gene-virus-mediated manganese superoxide dismutase effectively suppresses tumor growth in hepatocellular carcinoma in vitro and in vivo.
abstract: 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.
authors.affiliation: 1 School of Public Health, Zhejiang University , Hangzhou, China .
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.forename: Buyun
authors.initials: B
authors.lastname: Ma
authors.forename: Yigang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Xiao
authors.forename: Yanping
authors.initials: Y
authors.lastname: Kong
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhou
authors.forename: Dajing
authors.initials: D
authors.lastname: Xia
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics*; D020169:Caspases / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents; D013482:Superoxide Dismutase; D020169:Caspases
keywords: Mn-SOD; hepatocellular carcinoma; oncolytic adenovirus