8-氯腺苷对Molt-4细胞的生长抑制和凋亡诱导作用研究  

Growth Inhibition and Apoptosis Induced by 8 - Cloroadenosine in Molt - 4 Cells

作　　者：刘彦[1] 方家椿[1] 王耐勤 刘彤 苏虹 

机构地区：[1]北京医科大学临床肿瘤学院北京市肿瘤防治研究所,北京100034

出　　处：《中国医药导刊》2000年第6期37-40,共4页Chinese Journal of Medicinal Guide

基　　金：国家1035医药工程项目资助

摘　　要：目的:研究8-氯腺苷(8-Choroadenosine,8-Cl-Ado)对人T淋巴母细胞白血病细胞株Molt-4的生长和凋亡的作用,以及对相关基因和CREB结合活性的影响。方法:以不同浓度8-Cl-Ado处理体外培养的Molt-4细胞,采用MTT法测定药物半数抑制浓度(IC_(50)),用光学显微镜、流式细胞仪和琼脂糖电泳分析细胞凋亡,分别用斑点杂交法和免疫组化法观察c-mye和bcl-2的表达情况,用凝胶阻滞电泳检测CREB与DNA结合活性变化。结果:8-Cl-Ado可显著抑制Molt-4细胞的生长,IC_(50)为0.6μmol/L。8-Cl-Ado可诱导Molt-4细胞凋亡,细胞出现典型的凋亡形态学变化,流式细胞分析G_1期细胞数增加,S期细胞数减少并有亚G_1峰,琼脂糖电泳可见DNALadder出现,此外观察到c-myc基因表达瞬时增强和CREB结合活性的增强,但bcl-2基因表达无明显变化。结论:8-Cl-Ado能抑制Molt-4细胞的生长和诱导其凋亡,此生物学效应可能与c-myc瞬时表达增强及CREB结合活性增强有关。该药对molt-4细胞bcl-2基因表达无影响。Objective : To study the effect of growth inhibition and apoptosis induced by 8 - Chloroadenosine (8 - Cl -Ado) in Molt - 4 lymphoblasts cell line and observe the expression of c - myc gene and CREB binding activities with DNA. Methods: Molt - 4 ceDs were treated with 8 - Cl - Ado in different concentrations and growth inhibition was evaluated by MTT assay. Cell apoptosis was analyzed by light microscopy, flow cytometry and chromosome DNA fragmentation, the expression of c - myc and bcl - 2 were observed by dot blot or immunocytochemipal method. Results: 8 - C1 - Ado inhibited growth of Molt - 4 cells markedly, the IC50 is 0. 6μmol/L. 8 - Cl - Ado can induce apoptosis with characters of phenotypes, DNA ladder and DNA content change. Further study showed that these effects were time and concentration - dependent, 8 -Cl - Ado can increase c - myc expression, but it does not change the expression of bcl - 2. Gel Shift Assay demonstrated that there is an enhancement of CREB - DNA - binding activities when Molt - 4 ceils are treated with 8 - Choroadenosine. Conclusion: 8 - Cl - Ado can inhibit growth and induce apoptosis of Molt -4 cells, these effects are possibly relationship with the increases of c - myc expression and CREB binding activities.

关 键 词：氯腺苷 抑制生长 凋亡 抗肿瘤药 新药 

分 类 号：R73-36[医药卫生—肿瘤]