HSV-tk/ACV系统基因治疗小鼠黑色素瘤的实验研究

Gene Therapy of Mice Melanoma by HSV-tk/ACV System

本文首次应用HSV-tk/ACV系统对小鼠黑色素瘤B16进行了基因治疗研究。体外实验证实,转有HSV-tk基因的B16细胞(B16LNTK)对阿昔洛韦(Acyclovir,ACV)的敏感性显著高于其亲本细胞B16,当B16LNTK与B16以不同比例混合培养时,亲本细胞B16对ACV的敏感性不同程度增高,存在旁观者效应。用B16LNTK接种同系C57BL/6小鼠,经ACV治疗20天后,B16LNTK组小鼠的肿瘤(0.254±0.18cm^3)较对照组B16组的肿瘤(4.43±1.08cm^3)小94％(n=5,双侧t检验P<0.01)。HSV-tk/ACV系统原位基因转移治疗B16荷瘤小鼠效果显著:HSV-tk/ACV治疗组肿瘤14天后较对照组肿瘤小43％(n=5,双侧t检验P<0.05)。结果提示HSV-tk/ACV系统可作为黑色素瘤基因治疗研究的一种有效方法。

This is the first report on gene therapy of mice melanoma by HSV - tk/ACV system. The sensitivity to ACV of genetically modified B16 cells (B16LNTK) was much higher than that of the parental cells. The sensitivity to ACV of B16 cells was increased when they were co - cultured with B16LNTK cells with various ratios. which showed the exist of the by stander effects. The tumor volume of B16LNTK (0.25cm3) is 94% less than that of B16 in C57BL/6 mice after 20-days ACV treatment. (P< 0.01) . B16 tumor loaded mice were treated in situ with HSV-tk /ACV, a significant effect was obtained. The tumor volume of B16 decreased to 57% of its origin. (P < 0. 05) The above results showed the HSV - tk/ACV system is a promising method for gene therapy of mice melanoma.