神经胶质瘤基因治疗中旁观者效应的动物试验

In vivo studies of bystander effect in gene therapy to glioma

目的：探讨单纯疱疹病毒（ＨＳＶ）Ⅰ型胸苷激酶（ＴＫ）基因逆转录病毒载体生产细胞（ｐＬＴＫｃＳＮ／ＶＰＣ）和更昔洛韦（Ｇａｎｃｉｃｌｏｖｉｒ，ＧＣＶ）系统杀伤大鼠脑内神经胶质瘤细胞的旁观者效应。方法：用Ｃ６，Ｃ６ＸＳＮ，Ｃ６ＴＫ及不同比例的ＴＫ（＋）和ＴＫ（－）混合细胞接种于大鼠右侧额叶脑内，５ｄ后动物腹腔内注射ＧＣＶ溶液，剂量为１５ｍｇ／ｋｇ，每日２次，共１０ｄ。细胞接种后３周，所有动物处死，测量肿瘤大小，计算各组动物的肿瘤平均体积和成瘤率；肿瘤组织作病理检查。结果：５０％Ｃ６ＴＫ和１００％Ｃ６ＴＫ两组动物的成瘤率和肿瘤平均体积明显小于其余３组；病理检查发现５０％Ｃ６ＴＫ组动物肿瘤灶内有明显的病理改变。结论：旁观者效应在动物体内也能介导ＧＣＶ的杀伤作用；

Objective: To evaluate the bystander effect of pLTKcSN/VPC and ganciclovir (GCV) system killing glioma in vivo. Methods: An animal model was established by implanting tumor cells directly into fight frontal lobe. The cells implanted were 100% C6, 100% C6XSN, 10% C6TK/90% C6, 50% C6TK/50% C6 and 100% C6TK. Five days after cell implantation, all animals were given GCV 15 mg/kg, bid and three weeks later, all animals were sacrificed and the tumor size was measured. Results: The tumor sizes of the 50% C6TK and 100% C6TK groups were obviously smaller than those of the other 3 groups. Pathological study showed that the changes in tumors of C6TK and 50% C6TK were different from those of the other 3 groups. Conclusion: The results indicate that bystander effect can interfere formation and inhibit the growth of glioma in rats.