title: Antitumor effects of oncolytic adenovirus armed with Drosophila melanogaster             deoxyribonucleoside kinase in colorectal cancer.
abstract: Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK)             was applied as a cancer gene therapeutic approach. To improve the antitumor effect             of Dm-dNK, a novel suicide gene system based on an oncolytic adenovirus vector             was developed to produce therapeutic effects towards colorectal cancer cells.             We constructed an oncolytic adenoviral vector (ZD55), which was designed by deletion             of the E1B-55 kDa gene for selective replication in tumor cells, containing suicide             gene (Dm-dNK) driven by a cytomegalovirus promoter. We analysed the expression             and activity of Dm-dNK in colorectal cancer cells (HCT-116 and SW620) via reverse             transcription (RT)-PCR and enzyme assay. We assessed selective cytotoxic effects             of Dm-dNK with the presence of the analogs (E)-5-(2-bromovinyl)-2'-deoxyuridine             (BVDU), difluorodeoxycytidine (dFdC) or 1-β-D-arabinofuranosylthymine (ara-T)             by MTT and FACS; the variation of oncolytic adenovirus was detected by titer assay             and western blot analysis. Our data showed that ZD55-Dm-dNK mediated high expression             of Dm-dNK in HCT-116 and SW620 cancer cell lines and low levels of expression             in WI-38 and MRC-5 normal cells, strong cytotoxicity was observed only in tumor             cells after ZD55-Dm-dNK infection combined with nucleoside analogs (NA). When             ZD55-Dm-dNK was combined with BVDU or dFdC, it produced a synergistic inhibitive             effect of adenovirus replication while maintaining specific cancer cell killing             activity. The results suggest that the novel oncolytic virus ZD55-Dm-dNK, in combination             with NA, has potential as an efficient selective antitumoral agent and may produce             synergistic effects in safe control of adenovirus, which is a new promising therapeutic             for colorectal cancer.
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ma
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Qu
authors.forename: Liang
authors.initials: L
authors.lastname: Mao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhu
authors.forename: Lanling
authors.initials: L
authors.lastname: Jia
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000235:genetics / Q000628:therapy*; D003588:Cytopathogenic Effect, Viral; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D009705:Nucleosides / Q000378:metabolism / Q000494:pharmacology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D019076:Transgenes; D014779:Virus Replication / Q000187:drug effects
chemical_list: D009705:Nucleosides; D017853:Phosphotransferases (Alcohol Group Acceptor); C020018:deoxyribonucleoside kinases