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目的和方法:将可产生含有HSVTK基因逆转录病毒的包装细胞与BEL7402肝癌细胞混合后,接种于裸鼠皮下,复制肝癌模型。确定HSVTK基因转移后,给予动物注射GCV,观察HSVTK/GCV系统基因治疗实验性肝癌的在体疗效。结果:在体条件下,逆转录病毒可将HSVTK基因部分转导至肝癌细胞;GCV作用后,TK+中瘤细胞的生长受到明显抑制;电镜观察发现,GCV杀伤TK+肿瘤细胞的作用主要体现在细胞核;虽然组化染色分析表明TK基因转移效率只有10%~30%,但测量肿瘤体积显示HSVTK/GCV系统杀伤肝癌细胞的效果依然明显,故其作用机制可与“旁观者效应”有关。结论:HSVTK/GCV“自杀”基因系统有可能成为基因治疗肝癌的有效方法
Objective and method: The packaging cells containing HSVTK gene retrovirus were mixed with BEL7402 hepatoma cells and inoculated subcutaneously in nude mice to replicate the hepatoma model. After the HSV-TK gene transfer was determined, animals were injected with GCV to observe the in vivo efficacy of HSV-TK/GCV system gene therapy for experimental liver cancer. RESULTS: Under the in vivo condition, retrovirus could partially transduce HSVTK gene into hepatoma cells; after GCV, the growth of tumor cells in TK+ cells was significantly inhibited; electron microscopy showed that the role of GCV in killing TK+ tumor cells was mainly reflected in In the nucleus; although histological staining analysis showed that the TK gene transfer efficiency was only 10% to 30%, but the measurement of tumor volume showed that the effect of HSV TK/GCV system on killing hepatoma cells was still obvious, so its mechanism of action may be related to the “bystander effect”. related. Conclusion: HSVTK/GCV suicide gene system may be an effective method for gene therapy of liver cancer