Zhu, Z., Zhao, L., He, A., Huang, B., Karlsson, A., Xu, H., Zheng, X. (2010). Retrovirus-mediated Drosophila melanogaster Multisubstrate Deoxyribonucleoside Kinase Gene Therapy of Gastric Cancer Cells In Vitro and In Vivo.  Anticancer Res. 30(7): 2641--2649.

FBrf0211460

Research paper

The cytotoxicity of the Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK)/nucleoside analog system to human gastric carci-noma cells was evaluated in vitro and in vivo for the development of novel gene therapy for gastric cancer.MGC-803 and BGC-823 cells were infected with retroviral vectors containing the Dm-dNK gene expressing Dm-dNK in its active form. [(3)H]-labeled substrates were used for enzyme activity assays and cytotoxicities were evaluated in vitro by MTT assay and annexin-V-FITC labeled FACS methods. Bystander effect assay was performed by MTT assay using a mixture of cells with and without expressed Dm-dNK. Anti-tumor efficacy was also examined in vivo.Nucleoside analogs were significantly more cytotoxic to Dm-dNK-expressing cells than to their parental counterparts, and death was attributable to apoptosis. Implementation of the Dm-dNK/nucleoside analog system was associated with 'bystander' effects in vitro and suppressed the growth of MGC-803 tumors in mice.The Dm-dNK/nucleoside analoguesystem possesses significant potential as suicide gene therapy for human gastric carcinoma.