胞嘧啶脱氨基酶/5-氟胞嘧啶系统对人胰腺癌细胞恶性增殖的抑制作用

Cytosine Diaminase/5-Flurocytosine Mediated Inhibiting Effect on the Growth of Human Pancreatic Carcinoma Cells

目的 探讨大肠杆菌胞嘧啶脱氨基酶 (CD) / 5 -氟胞嘧啶 (5 - FC)系统对人胰腺癌细胞的体内外生长抑制作用。方法 将含 CD基因的重组逆转录病毒载体导入人胰腺癌细胞形成转化细胞系 ,对转化细胞进行体内外药物敏感实验 ,包括 :(1)计算转化细胞在前体药物 5 - FC作用下的细胞生长抑制率和克隆形成抑制率 ;(2 )MTT法检测旁观者效应 ;(3)观察 5 - FC对转化细胞裸鼠移植瘤的抑制作用。结果 转化细胞在 5 - FC作用下其生长抑制率为 80 .0 % ,克隆形成抑制率为 79.0 % ,均明显高于未转化细胞生长抑制率 4.8%和克隆形成抑制率5 .0 % (P<0 .0 1) ;混合细胞中含 10 %的转化细胞时 ,生长抑制率已达 5 0 .7% ;转化细胞的裸鼠移植瘤在 5 - FC作用下体积缩小。结论 CD/ 5 -

Objective To study the inhibition effect of E. coli cytosine diaminase (CD)/5flurocytosine (5FC) system on the growth of human pancreatic carcinoma cell line cells. Methods Recombinant retroviral vector expressing CD genes was transduced into pancreatic carcinoma cell line cells. In vitro and in vivo prodrug sensitivity assays were carried out, including: (1) detection of growth and colony forming inhibition rate of transduced cells in the presence of 5FC; (2) observation of bystander effect by MTT method; (3) observation of the growth inhibition effect of 5FC on transduced cell xenografts in nude mice. Results The growth and colony forming inhibition rate of the transduced cells in the presence of 5FC were 800% and 790%, which were obviously higher than 48% and 50% (P<001) of nontransduced cells. Mixed cells containing only 10% of transduced cells showed 507% reduction of proliferation (bystander effect). The growth of transduced cells xenografts could be totally regressed by 5FC. Conclusions CD/5FC system is a potential gene therapy strategy for pancreatic carcinoma.