逆转录病毒介导的CD/5-FC对胰腺癌细胞的杀伤作用

目的 :探讨大肠埃希菌胞嘧啶脱氨基酶 (CD) /5 -氟胞嘧啶 ( 5 FC)系统对胰腺癌细胞的体外生长抑制作用。方法 :将含CD基因的重组逆转录病毒载体导入胰腺癌细胞形成转化细胞系 ,对转化细胞进行体外药物敏感实验 ,包括 :1)转化细胞在前体药物 5 FC作用下的细胞生长抑制率 ;2 )MTT法检测旁观者效应。结果 :体外实验 5 FC的有效浓度 >2mmol/L时 ,就表现出杀伤作用 ,当 5 FC的有效浓度 >6mmol/L时 ,几乎未见细胞生长 ,PA3 17/CD与TD2混育比例在 90 %时 ,杀伤作用最大 ,相同药物浓度下 ,混育 96h杀伤作用明显高于 2 4h。结论 :CD/5 FC系统对胰腺癌细胞系细胞具有实验性基因治疗作用

Anti-pancreatic carcinoma effects resulting from cytosine deaminase gene delivered by retroviral vector

OBJECTIVE:To study the inhibition effect of E. coli cytosine diaminase (CD)/5-flurocytosine (5-FC) system on the growth of pancreatic carcinoma cell line cells. METHODS:Recombinant retroviral vector expressing CD genes were transduced into pancreatic carcinoma cell line cells. In vitro prodrug sensitivity assays were carried out, including: 1) detection of growth and colony forming inhibition rate of transduced cells in the presence of 5-FC; 2) observation of bystander effect by the MTT method.RESULTS:The efficient concentration range of 5-FC was less than 2 mmol/L. The TD2 /CD cells were nearly all dead when 5-FC was 6 mmol/L. When the mixture ratio of PA317/CD and TD2 was 90%, the tumor mortality was highest. The cell-killing efficacy when mixed 96 hrs was higher than that of 24 hrs. CONCLUSION:CD/5-FC system is a potential gene therapy strategy for pancreatic carcinoma.