胞嘧啶脱氨酶基因联合5-Fc治疗结肠癌的实验研究  

Experimental studies on the treatment of colon cancer by cytosine deaminase gene and 5-fluorocytosine

作　　者：黄建华[1] 王瑶[1] 李崇辉[2] 钟大光[1] 吕海燕[1] 

机构地区：[1]解放军总医院基础医学研究所免疫学研究室,北京100853 [2]解放军总医院肝胆外科研究所,北京100853

出　　处：《中华肿瘤杂志》2005年第1期6-8,共3页Chinese Journal of Oncology

基　　金：国家自然科学基金资助项目 (3 0 0 70 2 3 6)

摘　　要：目的　研究胞嘧啶脱氨酶基因 (CD)联合前体药物 5 氟胞嘧啶 (5 Fc)对结肠癌细胞的生长抑制作用。方法　应用逆转录病毒介导的方法 ,将逆转录病毒载体pLXSN中含有大肠杆菌CD基因的重组质粒pCD2 转染到病毒包装细胞PA317后 ,感染人结肠癌细胞株SW1116。对转基因的细胞进行RT PCR检测和体内外药物敏感实验。结果　获得了稳定表达EC CD基因的结肠癌细胞株SWCD2 ,与野生型SW1116细胞相比 ,SWCD2 细胞对基本无毒性的原药 5 Fc的敏感性增加 ,5 0 %细胞生长抑制率 (IC50 )浓度由野生型SW1116细胞的 16 0 0 0 μmol/L降低到SWCD2 的 6 6 μmol/L。经 5 Fc治疗后 ,SWCD2 细胞的裸鼠移植瘤生长明显缩小。结论　CD基因联合 5 Fc对人结肠癌细胞具有实验性基因治疗作用。Objective To investigate the effect of cytosine deaminase (CD) gene plus 5 fluorocytosine (5 Fc) on the growth of human colon cancer xenograft in nude mice. Methods Retroviral vector expressing CD gene was transfected into human colon cancer SW1116 cells. Expression of the transfected CD gene in SW1116 (SWCD 2) was confirmed by RT PCR. The cytotoxicity of 5 Fc on SW1116 was determined by MTT assay in vitro. In vivo, the CD gene expression vector was injected intratumorally and 5 Fc was given by ip injections. Results In vitro, SWCD 2 cells were killed by 5 Fc with an IC 50 of 66 μmol/L while the nontrasfected SW1116 cells needed an IC 50 of 16 000 μmol/L to be killed. The growth of SWCD 2 xenografts was significantly inhibited by systemic administration of 5 Fc. Conclusion CD gene /5 Fc system is a potential gene therapy strategy for human colon cancer. [

关 键 词：联合 胞嘧啶脱氨酶基因 CD基因 治疗 结肠癌细胞 人结肠癌 实验研究 重组质粒 稳定表达 逆转录病毒介导 

分 类 号：R735.35[医药卫生—肿瘤]