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　　瑞典研究人员最新发现，一种番茄基因与药物组合后能破坏癌细胞，这一发现将有助于用基因疗法治疗癌症。

　　瑞典隆德大学研究人员日前发表公报说，这种番茄基因在帮助建立和修复番茄基因组方面“非常活跃”，但它本身并不足以破坏癌细胞。在先后测试了不同药物后，研究人员最终发现，这种番茄基因与抗艾滋病药物AZT组合后，能更有效地打击癌细胞。

　　研究人员指出，很多人对基因疗法心存疑虑，担心病人的基因在接受治疗后发生改变，引发更多的不良反应。然而，上述研究并不存在这种风险，因为番茄基因仅仅被注入癌细胞内，并不影响其他细胞。

生物谷推荐原文出处：

Neuro Oncol. 2010 Feb 13 PMID: 20154339

Plant thymidine kinase 1: a novel efficient suicide gene for malignant glioma therapy.
Khan Z, Knecht W, Willer M, Rozpedowska E, Kristoffersen P, Clausen AR, Munch-Petersen B, Almqvist PM, Gojkovic Z, Piskur J, Ekstr?m TJ.

Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden (Z.K., P.M.A., T.J.E.); BioCentrum-DTU, Technical University of Denmark, Denmark (W.K., J.P.); ZGene A/S, H?rsholm, Denmark (M.W., P.K., Z.G.); Cell and Organism Biology, Lund University, Lund, Sweden (E.R., A.R.C., J.P.); Science, Systems and Models, Roskilde University, Roskilde, Denmark (B.M.-P.).

The prognosis for malignant gliomas remains poor, and new treatments are urgently needed. Targeted suicide gene therapy exploits the enzymatic conversion of a prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this therapeutic strategy has been considered a promising regimen for central nervous system (CNS) tumors, several obstacles have been encountered such as inefficient gene transfer to the tumor cells, limited prodrug penetration into the CNS, and inefficient enzymatic activity of the suicide gene. We report here the cloning and successful application of a novel thymidine kinase 1 (TK1) from the tomato plant, with favorable characteristics in vitro and in vivo. This enzyme (toTK1) is highly specific for the nucleoside analog prodrug zidovudine (azidothymidine, AZT), which is known to penetrate the blood-brain barrier. An important feature of toTK1 is that it efficiently phosphorylates its substrate AZT not only to AZT monophosphate, but also to AZT diphosphate, with excellent kinetics. The efficiency of the toTK1/AZT system was confirmed when toTK1-transduced human glioblastoma (GBM) cells displayed a 500-fold increased sensitivity to AZT compared with wild-type cells. In addition, when neural progenitor cells were used as delivery vectors for toTK1 in intracranial GBM xenografts in nude rats, substantial attenuation of tumor growth was achieved in animals exposed to AZT, and survival of the animals was significantly improved compared with controls. The novel toTK1/AZT suicide gene therapy system in combination with stem cell-mediated gene delivery promises new treatment of malignant gliomas.