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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.
OBJECTIVE: To investigate the effect of tissue-specific cytosine deaminase (CD) / 5-fluorocytosine (5-FC) on colorectal cancer cells LoVo and SW480 with different carcinoembryonicantigens (CEA) .Methods: Liposome method was used to transfect tissue-specific retroviral vector G1CEACDNa and non-tissue-specific retroviral vector pCD2 which were driven by CDS CEA gene cis-regulatory transcription sequence (TRS) into colorectal cancer LoVo and SW480 cells were screened by G418, and the prodrug 5-FC was amplified by G418.Results: The sensitivity of LoVo-CEACD and LoVo-CD to LoVo to 5-FC was significantly increased (P <0.01, t = SW480-CEACD and SW480-CD were significantly more sensitive to 5-FC than SW480 (P <0.01, t = 3.437, n = 9; P <0.01, t = 3.136, The sensitivity of LoVo-CEACD to LoVo-CD to 5-FC was significantly higher than that of LoVo-CD (P <0.05, t = 2.183, n = 9) The sensitivity of SW480-CD to SW480-CD was lower than that of SW480-SW480. The sensitivity of SW480-CEACD to prodrug 5-FC was lower than that of LoVo-CEACD (P <0.05, t = 2.504, n = 9) Obvious bystander effect can be observed.Conclusion: Tissue Heterosexual CD / 5-FC system LoVo and SW480 cells were significantly targeted killing effect, killing of SW480 cells but less than the LoVo cells.