CDglyTK自杀基因系统治疗小鼠慢性粒细胞白血病皮下移植瘤的研究  

Killing Effect of Double Suicide Genes Mediated by Retroviral Vector on K562 Cells

作　　者：姜义荣[1] 赖应昌[1] 陈小林[1] 万得胜[1] 陈万宁[1] 祁妙华[1] 刘春生[2] 陈学良[2] 马道新[2] 

机构地区：[1]东莞市人民医院血液内科,东莞523000 [2]山东大学齐鲁医院血液内科,济南250031

出　　处：《中国实验血液学杂志》2007年第1期47-51,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金资助(编号30070321);东莞市科技计划项目资助(编号200417)

摘　　要：为了探讨逆转录病毒介导的CDglyTK自杀基因系统对K562细胞的体内外杀伤作用,将逆转录病毒介导的CDglyTK自杀基因转染入K562细胞,体外实验用MTT法观察5-氟胞嘧啶/丙氧鸟苷(5-fluorocytosine/ganciclovir,5-FC/GCV)对K562/CDglyTK细胞的生长抑制率。体内实验时将K562/CDglyTK细胞和K562细胞接种于裸鼠皮下,使用GCV和5-FC后,观察裸鼠肿瘤体积的变化及裸鼠的生存率。体外实验表明,GCV联合5-FC对K562/CDglyTK细胞具有明显的杀伤作用;体内实验结果显示,皮下注射K562细胞和K562/CDglyTK细胞后小鼠成瘤率无明显区别;使用5-FC/GCV可明显抑制裸鼠体内的肿瘤形成;经5-FC/GCV治疗后K562/CDglyTK组的肿瘤体积较对照组明显缩小,裸鼠生存率也较对照组明显提高。结论:双自杀基因在体内外对K562细胞均有杀伤作用。The aim of study was to investigate the killing effect of double suicide gene system mediated by retroviral vector on K562 cells in vivo and ex vivo. CDglyTK gene was transfected into PA317 cells by using lipofectamine. K562 cells were infected with viral supernatant. K562 /CDglyTK cells were treated with 5-fluorocytosine （5-FC） and/or ganciclovir （GCV）. Mice were randomly divided into three groups： tumor formation, tumor inhibition and tumor therapy. Each mouse was implanted with K562/CDglyTK cells or K562 cells. The results indicated that the killing effect of 5-FC in combination with GCV on K562/CDglyTK was more significant than using 5-FC or GCV alone. In vivo study showed that after being injected subcutaneously with K562 cells and K562/CDglyTK cells, there was not obvious difference in tumor formation rate of mice, 5-FC ＋ GCV could suppress tumor formation of the K562/CDglyTK cells. After being treated with 5-FC and GCV, the median tumor volume of mice implanted with K562/CDglyTK cells decreased obviously, compared with the control group. Their median survival was significantly prolonged. It is concluded that double suicide genes are more effective for killing effect on K562 cells in vivo and in ex vivo. It may be applicable to clinical gene therapy.

关 键 词：双自杀基因 CDglyTK自杀基因 慢性粒细胞白血病 K562细胞 逆转录病毒载体 5-氟胞嘧啶 丙氧鸟苷 

分 类 号：R733.72[医药卫生—肿瘤] R979.1[医药卫生—临床医学]