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目的:研究HSVtk/GCV系统对腹水瘤的治疗作用.方法:采用XTT、动物实验、透射电镜和流式细胞仪等方法.结果:HSVtk(+)的P388tk细胞对GCV的敏感性约为其亲本P388细胞的37倍,且对其邻近的HSVtk(-)的P388细胞或S细胞具有旁观者效应,当P388tk细胞与P388细胞或S细胞混合培养,5μg/ml GCV处理后,P388tk细胞占混合细胞的10%,就可杀伤50%的混合细胞.动物实验中P388tk细胞或P388tk与P388细胞等量混合所致的荷瘤鼠在以CCV治疗后与对照组相比,肿瘤生长受到明显抑制,小鼠生存期明显延长;细胞死亡的机制与凋亡有关.结论:在体内和体外水平,HSVtk(+)的P388tk细胞能被GCV有效杀伤,且对其邻近的HSVtk(-)的细胞产生旁观者效应.
Objective: To study the therapeutic effects of HSVtk/GCV system on ascites tumors. METHODS: XTT, animal experiments, transmission electron microscopy and flow cytometry were used. Results: The sensitivity of HSVtk(+) P388tk cells to GCV was approximately that of their parents. P388 cells were 37-fold and had a bystander effect on P388 cells or S cells adjacent to HSVtk(-). When P388tk cells were mixed with P388 cells or S cells and treated with 5 μg/ml GCV, P388tk cells accounted for mixed cells. The 10% can kill 50% of mixed cells. In animal experiments, tumor growth was significantly inhibited in tumor-bearing mice caused by P388tk cells or P388tk mixed with P388 cells after treatment with CCV compared with the control group. The survival time of mice is significantly prolonged; the mechanism of cell death is related to apoptosis. Conclusion: HSVtk(+) P388tk cells can be effectively killed by GCV and produce bystanders to cells adjacent to HSVtk(-) in vitro and in vivo. effect.