CD基因对大肠癌杀伤作用的实验研究

目的：探讨ＣＤ基因对大肠癌靶向治疗的作用。方法：构建以ＣＥＡ基因顺式转录调控序列（ＴＲＳ）驱动ＣＤ基因的组织特异性重组逆转录病毒载体Ｇ１ＣＥＡＣＤＮa，脂质体裹 法将重组组织特异性载体pＣＤ２在逆转录病毒包装细胞ＰＡ３１７细胞中进行包装，收获病毒上清后分别转染入高分泌ＣＥＡ的大肠癌细胞ＬoＶo中，经Ｇ４１８筛选阳性克隆扩增后进行体外前药敏感实验及观察旁观者交应，然后再将转基因ＬoＶo细胞接种对裸鼠皮下成

Killing effects of cytosine deaminase (CD) gene on human colorectal carcinoma in vitro and in vivo

S Objective: To study the effect of CD gene specifically killing colorectal carcinoma cells. Methods: Recombinant retroviral vector G1CEACDNa, in which CEA promoter to promote CD gene, was constructed, and the retroviral construct and pCD2 were introduced to CEA highly producing colorectal carcinoma cell line LoVo, and then treated with 5 FC. LoVo cells transfected with G1CEACDNa gene, and pCD2 gene were injected s.c. into flanking nude mice, 5 FC was administrated i.p. At the end of the experiment, animals were sacrificed and the specimens were dehydrated in formalin and made into slides, then histopathological analysis was performed. Results: The LoVo cells transfered with G1CEACDNa gene displayed a higher antitumor effect than cells transfered with pCD2 gene. All mice developed tumors in 2 weeks after tumor cells implanted. When 500 mg/kg weight 5 FC was injected i.p., a significant anti tumor effects were observed in nude mice bearing CD(+) tumors, and tumors treated with 5 FC revealed different histopathological features compared with the control tumors. Conclusion: Suicide gene controlled by tissue specific promotor may result in obuious targeting antitumor effects.