Larsen N B, Munch-Petersen B, Piškur J
a Department of Biology , Lund University , Sweden.
Nucleosides Nucleotides Nucleic Acids. 2014;33(4-6):287-90. doi: 10.1080/15257770.2013.853781.
A promising suicide gene therapy system to treat gliomas has been reported: the thymidine kinase 1 from tomato (toTK1) combined with the nucleoside analog pro-drug zidovudine (azidothymidine, AZT), which is known to penetrate the blood-brain barrier. Transduction with toTK1 has been found to efficiently increase the sensitivity of human glioblastoma cells to AZT, and nude rats with intracranial glioblastoma grafts have shown significantly improved survival when treated with the toTK1/AZT system. We show in our paper that the strong suicidal effect of AZT together with toTK1 may be explained by reduced TTP-mediated feedback inhibition of the AZT phosphorylation.
据报道，一种有前景的用于治疗神经胶质瘤的自杀基因治疗系统：来自番茄的胸苷激酶1（toTK1）与核苷类似物前药齐多夫定（叠氮胸苷，AZT）联合使用，已知AZT可穿透血脑屏障。已发现用toTK1转导可有效提高人胶质母细胞瘤细胞对AZT的敏感性，颅内接种胶质母细胞瘤的裸鼠在用toTK1/AZT系统治疗后生存期显著延长。我们在论文中表明，AZT与toTK1共同产生的强烈自杀效应可能是由于TTP介导的对AZT磷酸化的反馈抑制作用减弱所致。
