HSVtk/GCV自杀基因系统治疗小鼠腹水瘤的研究

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.

Therapeutic Effects of HSVtk/GCV Suicide Gene System on Murine As-cites Tumors

Objective: To study the effect of HSVtk/GCV system on ascites tumors. Methods: Using the methods of modified XTT assay, animal experiment, transmission electron microscopy (TEM ) and flow cytometric ( FCM) assay. Results: The sensitivity of P388tk cell was about 37-fold than that of their patental P388 cell. Furthermore we found P388tk cells exhibited potent bystander killing. In vivo , the growth of tumors, which were produced by injecting P388tk cells or a mixture of 50% P388tk cells and 50% P388 cells into DBA/2 mice, was inhibited , furthermore mice survival periods were prolonged contrasted to control groups. Conclusion: HSVtk/GCV suicide gene system could effectively killed the HSVtk-gene-positive P388tk cells and nearby HSVtk-gene-negative cells by the bystander effect in vitro and in vivo.