【摘要】 目的:探讨HSV-TK/GCV自杀基因系统对小鼠乳腺癌细胞系MA782/5S-8102形成肿瘤的体内杀伤作用及其产生的旁观者效应。方法:体内实验分动物致瘤组、抑瘤实验组和治疗实验组。分别按实验组别要求接种5.0×106细胞/只于BALB/C小鼠的右腋窝皮下,观察各组肿瘤形成及肿瘤治疗情况并统计各组生存期。治疗结束后将标本制成石蜡切片进行病理学分析,RT-PCR检测HSV-TK基因在肿瘤组织中的表达情况。统计学处理采用SPSS软件进行完全随机的方差分析(ANOVA)。结果:实验结果显示小鼠成瘤率为100％。丙氧鸟苷(ganciclovir,GCV)可明显抑制MA782/5S-8102/TK细胞在BALB/C小鼠体内的肿瘤形成。经GCV治疗后,MA782/5S-8102/TK组和混合细胞组的肿瘤体积分别较对照组肿瘤体积缩小约36.7％和28.6％(均P<0.001);生存期也明显延长(P<0.001);RT-PCR检测HSV-TK基因在肿瘤组织中有表达。实验组肿瘤组织与对照组相比存在明显的病理学改变。结论:逆转录病毒可介导HSV-TK基因转入小鼠乳腺癌细胞MA782/5S-8102并获稳定表达,HSV-TK/GCV自杀基因系统在体内对乳腺癌细胞有杀伤作用,且存在明显的旁观者效应。更多还原

【Abstract】 Objective: To study in vivo killing effect and the bystander effect of HSV-TK/GCV suicide gene system on mice breast carcinoma cells MA782/5S-8102. Methods: The killing effects and bystander effects of HSV-TK/GCV system on breast carcinoma cells were studied in vivo. A total of 40 female BALB/C 6-8 weeks old mice were divi ded into three groups at random: tumors formation group. tumors inhibition groups and tumors therapy groups. Each mouse was implanted with 5. 0×106 MA782/5S-8102 or MA782/5S-8 102 /TK cells or cells mixed in right axilla. At the end of the experiment, mice were sacrificed and the specimens were processed for histopathological analysis. RT-PCR was applied to detect the expression of HSV-TK gene . Statistical analysis of the data was performed using the ANOVA(analysis of variance). Results: In in vivo study, the ratio of tumors formation is 100%. GCV could suppress tumor formation of the MA782/5S-8102/TK cells. After mice treated with GCV, the median tumor volume of mice implanted with MA782/ 5S-8102/TK cells and mice with cells mixed was respectively decreased to 63. 3% ( P<0. 001) and 71. 4% ( P<0. 001) compared with the control tumors. Their median survival was significantly prolonged( P<0.001). Tumors treated with GCV revealed different histopathological features compared with the control tumors. The expression of HSV-TK gene was detected by RT-PCR. Conclusion: The test showed that the HSV-TK gene can be transducted into mice breast cancer line MA782/5S-8102 under the mediation of retrovirus and be stably expressed, and HSV-TK/GCV suicide gene therapy system could improve the antitumoral efficiency. The bystander effect could be observated in HSV-TK/GCV system in vivo.更多还原