Expression of the bacterial nitroreductase enzyme in mammalian cells renders them selectively sensitive to killing by the prodrug CB1954
Expression of the bacterial nitroreductase enzyme in mammalian cells renders them selectively sensitive to killing by the prodrug CB1954
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DOI：
10.1016/0959-8049(95)00436-x
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发表时间：
1995-12-01
影响因子：
8.4
通讯作者：
Collins, MK
中科院分区：
文献类型：
--
作者：
Bridgewater, JA;Springer, CJ;Collins, MK
利用一种编码大肠杆菌硝基还原酶（NTR）的重组逆转录病毒感染哺乳动物细胞。表达NTR的NIH3T3细胞被前药CB1954杀死，NTR将CB1954转化为双功能烷基化剂。诚然，未经修饰的NIH3T3细胞也可能被杀死。与单纯疱疹病毒（HSV）胸苷激酶(TK)/更昔洛韦（GCV）酶/前药系统相比，NTR/CB1954对非循环细胞有效。CB1954和GCV联合作用于同时表达NTR和TK的细胞时，观察到协同杀伤。人类黑色素瘤、卵巢癌或间皮瘤细胞中NTR的表达也使它们对GB1954杀伤敏感。这些数据表明，将NTR基因传递到人类肿瘤，然后用CB1954治疗，可能提供一种新的肿瘤基因治疗方法。
A recombinant retrovirus encoding E. coli nitroreductase (NTR) was used to infect mammalian cells. NIH3T3 cells expressing NTR were killed by the prodrug CB1954, which NTR converts to a bifunctional alkylating agent. Admitted, unmodified NIH3T3 cells could also be killed. In contrast to the Herpes simplex virus (HSV) thymidine kinase (TK)/ganciclovir(GCV) enzyme/prodrug system, NTR/CB1954 cell killing was effective in non-cycling cells. Co-operative killing was observed when cells expressing both NTR and TK were treated with a combination of CB1954 and GCV. NTR expression in human melanoma, ovarian carcinoma or mesothelioma cells also rendered them sensitive to GB1954 killing. These data suggest that delivery of the NTR gene to human tumours, followed by treatment with CB1954, may provide a novel tumour gene therapy approach.