Department of Surgical Oncology, Department of General Surgery, First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang 110001, P.R.China.
Anticancer Res. 2010 Jul;30(7):2641-9.
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.
评估黑腹果蝇多底物脱氧核苷激酶（Dm-dNK）/核苷类似物系统对人胃癌细胞的细胞毒性，为胃癌的基因治疗开发提供新的方法。
用含有表达 Dm-dNK 的活性形式的逆转录病毒载体感染 MGC-803 和 BGC-823 细胞。用 [(3)H]-标记的底物进行酶活性测定，并用 MTT 法和流式细胞术检测 Annexin-V-FITC 标记的细胞凋亡。通过 MTT 法检测表达 Dm-dNK 的细胞和未表达 Dm-dNK 的细胞混合物的旁观者效应。还在体内检测了抗肿瘤功效。
核苷类似物对表达 Dm-dNK 的细胞比其亲本细胞具有更高的细胞毒性，且死亡归因于细胞凋亡。Dm-dNK/核苷类似物系统的实施与体外旁观者效应相关，并抑制了小鼠中 MGC-803 肿瘤的生长。
Dm-dNK/核苷类似物系统作为自杀基因治疗人类胃癌具有显著的潜力。
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