G-四链体配体Tel03诱导小鼠模型白血病瘤体细胞凋亡  

Induction of Apoptosis of Leukemic Tumor Cells in Mouse Model with G-quadruplex Ligand Tel03

作　　者：褚彬[1] 张英[2] 刘红星[3] 白砚霞[1] 左杏果[1] 陆敏秋[1] 吴梦青[1] 石磊[1] 刘蕾[1] 朱平[2] 

机构地区：[1]北京积水潭医院血液科,北京100035 [2]北京大学第一医院血液研究室,北京100034 [3]北京道培医院血液研究室,北京100049

出　　处：《中国实验血液学杂志》2010年第1期57-60,共4页Journal of Experimental Hematology

基　　金：科技部国际科技合作重大项目;编号2006DFB31430;国家863资源环境技术领域重点项目;编号2008AA062503

摘　　要：在体外研究发现酰亚胺类G-四链体配体Tel03能够诱导K562白血病细胞凋亡。本研究进一步用动物实验探讨Tel03的体内抗白血病瘤体细胞作用。建立裸鼠K562白血病瘤体模型,将实验用小鼠随机分为实验组和对照组,实验组分别腹腔注射等体积(300μl)含有不同剂量(5mg/kg和15mg/kg)Tel03药液的2组动物,对照组注射等量灭菌PBS,每周2次,连续4周。观察各组瘤体体积和动物体重,采用缺口末端标记技术(TUNEL法)检测瘤体细胞凋亡,Western blot检测Bcl-2和Bax的表达。结果表明:Tel03显著抑制动物白血病瘤体细胞的生长,实验组与对照组相比,瘤体均显著缩小,并且在小剂量组(5mg/kg Tel03)中Tel03诱导瘤体细胞凋亡的同时对动物不产生明显毒性作用。蛋白水平分析证实,Tel03抑制bcl-2表达同时诱导bax表达。结论:G-四链体配体Tel03具有诱导白血病瘤体细胞凋亡的作用,有用于白血病治疗的可能性。This study was aimed to investigate the anti-leukemia activity of Tel03 in vivo. The K562 xenografted leukemia model was established and mice were divided randomly into three groups. Mice of different group were treated with PBS （control）, 5 mg/kg Tel03 or 15 mg/kg Tel03 （ip,twice a week） respectively. Tumor volume, body weight and other behavior were observed regularly. Cell apoptosis was detected with TUNEL assay and the expression levels of Bcl-2 and Bax were detected by Western blot. The results indicated that Tel03 exerted anti-leukemia activity in mouse model. Tel03 significantly reduced tumor volume in Tel03-treated group compared with control. In addition, 5 mg/kg Tel03 induced cell apoptosis without exerting apparent toxicity in mice. After Tel03 treatment, the expression of Bcl-2 was inhibited; however, the expression of Bax was up-regulated. It is concluded that G-quadruplex ligand Tel03 can induce cell apoptosis in leukemia mouse model, and this agent may be a potential anticancer drug.

关 键 词：G-四链体配体 白血病 细胞凋亡 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]