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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。
OBJECTIVE: To investigate the in vivo killing effect of HSV-TK / GCV suicide gene system on mouse breast cancer cell line MA782 / 5S-8102 and its bystander effect. Methods: In vivo experiments were divided into animal tumor-bearing group, tumor-inhibiting experimental group and treatment experimental group. The mice were inoculated intraperitoneally with 5.0 × 10 6 cells / subcutaneous right axillary subcutaneous of BALB / C mice respectively according to the experimental group. The tumor formation and tumor treatment were observed in each group and the survival of each group was calculated. After the treatment, the specimens were made into paraffin sections for pathological analysis, and the expression of HSV-TK gene in the tumor tissues was detected by RT-PCR. Statistical analysis SPSS software was used for a complete randomized analysis of variance (ANOVA). Results: The experimental results showed that the rate of tumor formation in mice was 100%. Ganciclovir (GCV) significantly inhibited the tumor formation of MA782 / 5S-8102 / TK cells in BALB / C mice. The tumor volume of MA782 / 5S-8102 / TK group and mixed cell group decreased by 36.7% and 28.6% (all P <0.001) compared with that of control group after GCV treatment. The survival time was also significantly prolonged (P <0.001) The expression of HSV-TK gene was detected by RT-PCR in tumor tissue. There were obvious pathological changes in the experimental group compared with the control group. CONCLUSION: HSV-TK gene can be transduced into mouse mammary cancer cells MA782 / 5S-8102 by retrovirus and stably expressed. The HSV-TK / GCV suicide gene system has a killing effect on breast cancer cells in vivo, and there is obvious Bystander effect.