了解HSV-tk/GCV系统协同放射治疗对小鼠黑色素瘤的联合杀伤作用。方法：通过逆转录病毒介导，将潮霉素磷酸转移酶和HSV-tk的融合基因（hytk）导入黑色素瘤细胞中并获得表达，通过体外和C57BL/6小鼠动物实验，检测GCV对转基因细胞的体内外杀伤作用及联合应用放射治疗对黑色素瘤的治疗作用。结果： PCR、RNA Dot blotting、免疫组化检测证实HyTK在转基因细胞的表达，体内外实验示GCV对B16/HyTK细胞有明显的杀伤作用，而对野生型B16细胞无明显杀伤作用（P＜0.05）；联合应用低剂量GCV可使转入hytk基因的黑色素瘤细胞对放疗的敏感性明显增高（SER=1.62），体内实验也证实协同疗法可延缓荷瘤小鼠的肿瘤生长。结论： HSV-tk/GCV系统协同放射治疗有望成为黑色素瘤基因治疗的一种有效方法。

To evaluate the therapeutic efficacy of retroviral-mediated HSV-tk/GCV system combined with radiotherapy on murine melanoma. Methods: By using retroviral-mediated gene transfer technique， hygromycin phospotransferase-thymidine kinase fusion gene(hytk) was transferred into B16 murine melanoma cells. Antitumor effects were observed after γ-rays irradiation with 60 Co rays as well as GCV treatment. Growth inhibition of melanoma models in C57BL/6 mice by HSV-tk/GCV systems in combination with radiotherapy was observed. Results: B16 cells transduced with hytk gene and treated with low concentrations of GCV， which showed little cytotoxicity alone， were highly sensitive to radiation. The sensitizer enhancement ratio(SER) was 1.62. This radiopsensitization was also obtained in vivo. Conclusion： The addition of retroviral-mediated HSV-tk/GCV gene therapy to standard radiation therapy an improve the therapeutic effectiveness for melanoma.

* 本课题为福建省科委基金（99-Z-167）资助