摘要
目的:探讨组织特异性胞嘧啶脱氨基酶(cytosinedeaminase,CD)/5-氟胞嘧啶(5-fluorocytosine,5-FC)系统对不同分泌癌胚抗原(carcinoembryonicantigen,CEA)的大肠癌细胞LoVo和SW480的靶向杀伤作用.方法:脂质体法将CEA基因顺式转录调控序列(TRS)驱动CD基因的组织特异性逆转录病毒载体G1CEACDNa及非组织特异性逆转录病毒载体pCD2分别转导入大肠癌细胞LoVo和SW480,以G418筛选阳性克隆扩增后给予前药5-FC进行敏感试验.结果:LoVo-CEACD及LoVo-CD比LoVo对5-FC的敏感性明显提高(P<0.01,t=5.688,n=9;P<0.01,t=3.136,n=9),SW480-CEACD及SW480-CD比SW480对5-FC的敏感性明显提高(P<0.01,t=3.437,n=9;P<0.01,t=3.516,n=9),LoVo-CEACD比LoVo-CD对5-FC的敏感性明显增强(P<0.05,t=2.183,n=9),而SW480-CEACD对5-FC的敏感性小于SW480-CD,SW480-CEACD对前药5-FC的敏感性低于LoVo-CEACD(P<0.05,t=2.504,n=9),转CD基因之LoVo和SW480细胞体外实验均可观察到明显的旁观者效应.结论:组织特异性CD/5-FC系统对LoVo和SW480细胞均有明显的靶向杀伤效果,但对SW480细胞的杀伤作用小于LoVo细胞.
AIM:To investigate the killing effect of carcinoembryonic antigen (CEA) and tissue-specific cytosine deaminase (CD)/5- fluorocytosine (5-FC) system on human colorectal carcinoma cell lines LoVo and SW480 in vitro. METHODS:Recombinant retroviral vector G1CEACDNa was constructed,in which the CD gene was controlled under the CEA promoter, and retroviral vector pCD2 were introduced through liposome technique respectively to the human colorectal carcinoma cell lines LoVo and SW480. Expression of CEA was high and low in both the cell lines respectively. The cells were selectively cultured in G418. The proliferative colonies were treated with 5-FC. RESULTS:After the transfection, LoVo-CEACD cells and LoVo-CD cells were more sensitive to 5-FC than their parental cells (P <0.01, t =5.688, n =9; P <0.01, t =3.136, n =9), and SW480-CEACD cells and SW480-CD cells were more sensitive than their parental cells as well (P <0.01,t =3.437,n =9;P <0.01, t =3.516, n =9). Furthermore, the LoVo-CEACD cells were more sensitive to 5-FC than the LoVo-CD cells (P <0.05, t =2.183,n =9) while the SW480-CEACD cells were less sensitive than SW480-CD cells.The LoVo-CEACD cells displayed a higher anti-tumor effect than SW480-CEACD cells in vitro. The bystander effect in all cells transfected with CD gene were observed in this study. CONCLUSION:The CEA tissue-specific CD/5-FC systemdisplays an obvious targeting anti-tumor effect on human colorectal carcinoma cell lines LoVo and SW480, but the killing effect on the LoVo-CEACD cells is higher than that on the SW480-CEACD cells in vitro.
出处
《世界华人消化杂志》
CAS
2003年第5期535-539,共5页
World Chinese Journal of Digestology
