Zhang, N., Dong, X., Sun, Y., Cai, X., Zheng, C., He, A., Xu, K., Zheng, X. (2013). Cytotoxic effects of adenovirus- and lentivirus-mediated expression of Drosophila melanogaster deoxyribonucleoside kinase on Bcap37 breast cancer cells.  Oncol. Reps 29(3): 960--966.

FBrf0220625

Research paper

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.