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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SW4 80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SW4 80 ,以G4 18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 .0 1,t=5 .6 88,n =9;P <0 .0 1,t=3.136 ,n =9) ,SW4 80 CEACD及SW4 80 CD比SW4 80对 5 FC的敏感性明显提高 (P <0 .0 1,t=3.4 37,n=9;P <0 .0 1,t=3.5 16 ,n =9) ,LoVo CEACD比LoVo CD对 5 FC的敏感性明显增强 (P <0 .0 5 ,t=2 .183,n =9) ,而SW4 80 CEACD对 5 FC的敏感性小于SW4 80 CD ,SW4 80 CEACD对前药 5 FC的敏感性低于LoVo CEACD(P <0 .0 5 ,t=2 .5 0 4 ,n =9) ,转CD基因之LoVo和SW4 80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SW4 80细胞均有明显的靶向杀伤效果 ,但对SW4 80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 the proliferation of colon cancer cells LoVo and SW480 with different carcinoembryonicantigens (CEA) Methods: Liposome-mediated transfection of tissue-specific retroviral vector G1 CEACDNa and non-tissue specific retroviral vector pCD2 of CDS-driven CEA gene into colorectal cancer cells LoVo and SW480, G418-positive clones were amplified and prodrug 5 FC was tested for sensitivity.Results: The sensitivity of LoVo CEACD and LoVo CD to LoVo to 5 FC was significantly increased (P <0.01, t = 5). The sensitivity of SW4 80 CEACD and SW4 80 CD to SW480 to 5 FC was significantly higher than that of SW4 80 (P <0.01, t = 3.136, n = 9) = 3.437, n = 9; P <0.01, t = 3.516, n = 9). The sensitivity of LoVo CEACD to LoVo CD to 5 FC was significantly enhanced (P <0.05, t = 2). 183, n = 9). The sensitivity of SW4 80 CEACD to 5 FC was less than that of SW4 80 CD, and the sensitivity of SW4 80 CEACD to prodrug 5 FC was lower than that of LoVo CEACD (P <0.05, t = 2.5 0 4, n = 9), turn the CD gene Significant bystander effect was observed in LoVo and SW480 cells in vitro.Conclusion: Tissue-specific CD5-FC system has obvious targeted killing effect on LoVo and SW480 cells, but its killing effect on SW480 cells is less than LoVo cells.