摘要
目的：研究单纯疱疹病毒胸苷激酶基因联合丙氧鸟苷（ Ｈ Ｓ Ｖｔｋ／ Ｇ Ｃ Ｖ） 系统对实体瘤的治疗作用。方法：以感染法建立携带 Ｈ Ｓ Ｖｔｋ 基因的 Ｐ３８８ｔｋ 细胞，用 Ｘ Ｔ Ｔ、动物实验、透射电镜和流式细胞仪（ Ｆ Ｃ Ｍ） 方法研究 Ｇ Ｃ Ｖ 对 Ｐ３８８ｔｋ 细胞的杀伤作用及其机制。结果： Ｐ３８８ｔｋ 细胞对 Ｇ Ｃ Ｖ 的敏感性明显增强，约为其亲本 Ｐ３８８ 细胞的３７ 倍，且当 Ｐ３８８ｔｋ 细胞与 Ｐ３８８ 细胞或 Ｓ 细胞混合培养经５ μｇ·ｍｌ－ １ Ｇ Ｃ Ｖ 处理后， Ｐ３８８ｔｋ 细胞占总细胞的１０ ％ ，可杀伤５０ ％ 的混合细胞。动物实验中， Ｐ３８８ｔｋ 细胞或 Ｐ３８８ｔｋ 细胞与 Ｐ３８８ 细胞等量混合所致的荷瘤鼠在以 Ｇ Ｃ Ｖ 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；细胞死亡的机制可能与凋亡有关。结论： Ｈ Ｓ Ｖｔｋ（ ＋ ） 的 Ｐ３８８ｔｋ 细胞能被 Ｇ Ｃ Ｖ 有效杀伤，且对其邻近的 Ｈ Ｓ Ｖｔｋ（ － ） 的细胞产生旁观者效应。
Objective:The experiment was designed to study the effect of herpes simplex virus thymidine kinase combined with ganciclovir (HSVtk/GCV) system on solid tumors. Method:After establishment of HSVtk?gene?positive P388tk cells using the method of infection, the sensitivity of P388tk cells to GCV and the killing mechanism of the system were evaluated by the 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. Fifty percents of mixed population were killed in the presence of 5?μg·ml -1 GCV when the P388tk cells reached 10% in total cell population. In vivo , the growth of tumors, which were produced by injecting P388tk cells or a mixture of 50% P388tk cells and 50% P388 cells s.c. into DBA/2 mice, was inhibited , and the mice survival period was prolonged contrasted to control groups.Conclusion:HSVtk/GCV suicide gene system could effectively kill the HSVtk?gene?positive P388tk cells and nearby HSVtk?gene?negative cells by the bystander effect.
出处
《南京铁道医学院学报》
1999年第3期155-157,共3页
Journal of Nanjing Railway Medical College
基金
铁道部科技基金
关键词
HSVtk
GCV
实体瘤
白血病细胞
治疗
herpes simplex virus thymidine kinase gene
ganciclovir
solid tumor
leukemia cells
mice
