title: Cytotoxic effects of adenovirus- and lentivirus-mediated expression             of Drosophila melanogaster deoxyribonucleoside kinase on Bcap37 breast cancer             cells.
abstract: Gene transfer using different viral vectors has demonstrated different antitumor             effects in suicide gene therapy. In the present study, in order to optimize the             efficacy of replication-defective adenoviral and lentiviral vectors for gene therapy,             RT-PCR was used to evaluate the expression of Drosophila melanogaster deoxyribonucleoside             kinase (Dm-dNK) in the Bcap37 human breast cancer cell line, dThd was used to             determine the activity of Dm-dNK, cell cytotoxicity was evaluated by MTT assay             and cell proliferation was assessed using a hemocytometer. Moreover, apoptosis             induction was evaluated by the Annexin V-FITC-labeled FACS method. Furthermore,             BALB/C nude mice bearing tumors were treated with Dm-dNK mediated with the pyrimidine             nucleoside analog, brivudine [BVDU, (E)-5-(2-bromovinyl)-2'-deoxyuridine]. Our             results indicated that the gene expression of Dm-dNK transfected by adenoviral             and lentiviral vectors may be detected and that its long-term activity may be             retained. Both vectors containing the Dm-dNK gene revealed high cytotoxicity and             sensitized cell apoptosis from the BVDU prodrug. In tumor models, lentivirus-mediated             gene therapy significantly inhibited the growth of tumors compared with adenovirus-mediated             gene therapy. Although adenovirus- and lentivirus-transduced Dm-dNK reveal strong             treatment efficacy in vitro, the latter has great potential due to the long-term             expression of the therapeutic gene in vivo.
authors.affiliation: Department of Surgical Oncology, Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, PR China.
authors.forename: Nianqu
authors.initials: N
authors.lastname: Zhang
authors.forename: Xiaoshen
authors.initials: X
authors.lastname: Dong
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Sun
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Cai
authors.forename: Caiwei
authors.initials: C
authors.lastname: Zheng
authors.forename: Anning
authors.initials: A
authors.lastname: He
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis* / Q000235:genetics; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology; D000091402:Prohibitins; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D029721:Drosophila Proteins; C000717331:PHB2 protein, human; C000717333:Phb2 protein, mouse; D011355:Prodrugs; D000091402:Prohibitins; C020235:brivudine; D017853:Phosphotransferases (Alcohol Group Acceptor); C020018:deoxyribonucleoside kinases; D001973:Bromodeoxyuridine