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“自杀基因”疗法应用于肿瘤治疗时,通常是在肿瘤局部直接转染“自杀基因”,以期达到在肿瘤局部发挥抗肿瘤作用而避免全身毒性.在本实验中,我们观察了腺病毒介导的“自杀基因”疗法(CD/5FC系统)对人肝细胞癌SMMC-7721及小鼠结肠腺癌CT26的生长抑制作用,证实了腺病毒介导的CD/5FC系统在体外能杀伤人肝癌细胞SMMC-7721,并且能明显地抑制裸鼠SMMC-7721肿瘤模型的生长,对小鼠的结肠腺癌CT26也有一定的治疗作用.同时观察了以AFP启动子驱动的CD基因合并5FC的使用对AFP阳性肝癌细胞的特异性杀伤作用,证实了以肝癌特异启动子驱动的CD基因能在高表达AFP的肝癌细胞HepG2中特异表达,合并5FC的使用能在体外特异地杀伤HepG2细胞.这一组织特异性的“自杀基因”系统能特异地抑制高水平分泌AFP的人肝细胞癌裸鼠模型7721AFP(+)的生长,上述研究结果表明,腺病毒介导的CD/5FC系统是一个有效的治疗方案,组织特异性的表达调控更能体现该疗法的实用价值.
When “suicide gene” therapy is applied to tumor therapy, it is usually directly transfected with a “suicide gene” in the tumor site to achieve an anti-tumor effect at the tumor site to avoid systemic toxicity. In this experiment, we observed adenovirus-mediated treatment. The inhibition effect of the “suicide gene” therapy (CD/5FC system) on human hepatocellular carcinoma SMMC-7721 and mouse colon adenocarcinoma CT26 confirms that adenovirus-mediated CD/5FC system can kill human hepatoma cells in vitro. SMMC-7721 can significantly inhibit the growth of SMMC-7721 tumor model in nude mice, and also has a certain therapeutic effect on mouse colon adenocarcinoma CT26. At the same time, the use of the AFP promoter-driven CD gene and 5FC for AFP was observed. The specific killing effect of positive hepatocellular carcinoma cells confirmed that the CD gene driven by hepatocarcinoma-specific promoter can be specifically expressed in hepatocellular carcinoma cell HepG2 highly expressing AFP, and the use of 5FC combined can specifically kill HepG2 cells in vitro. The “suicide gene” system can specifically inhibit the growth of high-level human hepatocellular carcinoma nude mice model 7721AFP(+) that secretes AFP. The above results indicate that adenovirus-mediated CD/5FC system An effective treatment options, tissue-specific expression regulation to better reflect the practical value of the therapy.