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在恶性肿瘤细胞中转入的胸苷激酶基因表达并激活抗病毒药物,从而治疗恶性肿瘤在近年来被看作恶性肿瘤基因治疗的有力手段之一.这类抗病毒药物能通过破坏DNA分子结构的完整性而作用于病毒或增殖的细胞,提示人们它们能否作为放疗增敏剂使用.本文采用嘧啶类似物BVdUrd作为治疗药物,以U-251神经胶质瘤细胞作为靶细胞.U-251用携带HSV-tk基因的逆转录病毒载体GITkSvNa.53转染,并经G418筛选.得到已转入HSV-tk基因的细胞U-251-tk.U-251-tk用5000Ci ~(137)Cs源照射(1.61Gy/min),结果发现BVdUrd20-200μg/ml单剂量在8Gy照射前24h或照射后24h与细胞共孵育能够显著地增强射线对U-251-tk肿瘤细胞的杀伤作用,当BVdUrd浓度为40μg/ml、照射前24h用药,与未转染HSV-tk的U-251细胞相比,U-251-tk细胞被杀伤的数量增加近一倍.结果提示,HSV-tk基因的存在是BVdUrd作为放疗增敏剂的必需条件,BVdU可能通过影响DNA的完整性从而使DNA分子容易被射线破坏且不利于其修复.实验结果表明在应用HSV-tk基因转染治疗神经胶质瘤时辅助以放射治疗可以得到较好的治疗效果.
In recent years, malignant tumors have been considered as one of the powerful tools for the gene therapy of malignant tumors by expressing thymidine kinase gene and activating antiviral drugs in malignant cells, and such antiviral drugs can destroy DNA molecular structure Of the integrity of the role of the virus or proliferating cells, suggesting that they can be used as radiosensitizers in this article pyrimidine analog BVdUrd as a therapeutic drug to U-251 glioma cells as a target cell U-251 Transfected with the retroviral vector GITkSvNa.53 carrying HSV-tk gene and screened by G418, the cells transfected with HSV-tk gene U-251-tk.U-251-tk were transfected with 5000Ci ~ (137) Cs (1.61Gy / min). The results showed that single dose of BVdUrd20-200μg / ml could significantly enhance the killing of U-251-tk tumor cells by single dose of BVdUrd20-200μg / ml 24h before irradiation or 24h after irradiation. When BVdUrd The number of U-251-tk cells was almost doubled in U251 cells transfected with HSV-tk at a concentration of 40μg / ml for 24 hours before irradiation.The results suggest that the presence of HSV-tk gene Is a necessary condition for BVdUrd as radiosensitizer, BVdU may affect the DNA So that the whole of the DNA molecules is easily destroyed and not conducive to their ray repair. Auxiliary results show that radiation therapy can be a better therapeutic effect in the application of HSV-tk gene transfected glioma therapy.