title: Combined use of adenoviral vector Ad5/F35-mediated APE1 siRNA enhances the therapeutic efficacy of adenoviral-mediated p53 gene transfer in hepatoma cells in vitro and in vivo.
abstract: Gene therapy has emerged as a novel therapeutic approach for the treatment of cancer. In order to establish a more effective therapeutic strategy against unresectable hepatocellular carcinoma (HCC), we evaluated, in the present study, the effects of combined treatment with adenoviral vector Ad5/F35-mediated APE1 siRNA (Ad5/F35-siAPE1) and adenoviral-mediated p53 gene transfer (Ad-p53) in hepatoma cells in vitro and in vivo. Infection of SMMC-7721 cells with Ad5/F35-siAPE1 resulted in a time- and dose-dependent decrease of APE1 protein, while Ad-p53 treatment led to a time- and dose-dependent increase of p53 protein expression. Ad5/F35-siAPE1 significantly enhanced the cytotoxic effect of SMMC-7721 cells to Ad-p53 in cell survival assays, associated with increased cell apoptosis. Moreover, administration of Ad5/F35-siAPE1 and Ad-p53 into nude mice resulted in tumor growth inhibition and apoptosis induction in SMMC-7721 xenografts compared to administration of either agent alone. These results suggest that combination of Ad5/F35-siAPE1 and Ad-p53 could be a promising gene therapeutic approach against human HCC.
authors.affiliation: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Cun
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.forename: Mengxia
authors.initials: M
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Dai
authors.forename: Shiheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics*; D014161:Transduction, Genetic; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase