羟基脲联合干扰素-α对K562细胞生长及凋亡相关基因表达的影响  

Effect of hydroxyurea combined with interferon-alpha on growth and apoptosis-related oncogene expression of K562 cells

作　　者：陈汉春[1] 罗志勇[1] 罗赛群[1] 汤立军[1] 彭兴华[1] 李晓林[2] 

机构地区：[1]湖南医科大学分子生物学研究中心,长沙410078 [2]湖南医科大学附属湘雅医院血液科,长沙410078

出　　处：《中华医学杂志》2000年第8期606-609,共4页National Medical Journal of China

基　　金：国家自然科学基金!资助项目 (39570 80 5)

摘　　要：目的　观察羟基脲 (HU)及HU联合干扰素 α(IFN α)对慢性粒细胞性白血病 (CML)细胞株—K5 6 2细胞增殖、死亡及其相关基因表达的影响 ,进一步探讨化疗药物与细胞因子联合治疗CML的分子基础。方法　细胞计数及台盼蓝染色分析细胞增殖与存活率 ;逆转录 聚合酶链反应 (RT PCR)分析 48h培养后的K5 6 2细胞中bcr abl、bax及c myc基因表达水平。结果　HU及HU联合IFN α均抑制细胞增殖和促进细胞死亡 ;与对照组比较 ,HU可以显著抑制bcr abl基因表达 (下调 17.5 % )和促进bax基因表达 (上调 12 .0 % ) ;IFN α呈剂量依赖性协同HU调节bcr abl(下调 35 .7% )和bax(上调 15 % )基因表达水平 ;HU及HU联合IFN α对c myc基因表达均呈现轻微抑制效应。结论　从调节细胞平衡的相关基因的表达水平进一步阐明了HU联合IFN α作用于白血病细胞的分子机制。Objective To observe the effect of hydroxyurea (HU) alone and in combination with interferon alpha (IFN α) on the cell growth and cell death, and the related oncogene expression of chronic myelogenous leukemia (CML) cell line, K562 cells. To further investigate the molecular basis of combination therapy on CML by chemotherapeutants combined with cytokines. Methods The proliferation and viability of K562 cells were detected by cell counting and trypan blue dye exclusion test. The levels of bcr abl, bax and c myc gene expression in K562 cells incubated for 48 hours were examined using RT PCR technique. Results Cell proliferation was suppressed and cell death process was accelerated by both HU and HU combined with IFN α. HU significantly inhibited bcr abl gene expression and increased bax gene expression level (both P <0.05 as compared with that of control). Furthermore, IFN α dose dependently enhanced the regulatory effects of HU on bcr abl and bax gene expression. HU alone and in combination with IFN α suppressed slightly c myc gene expression. Conclusions Both HU and HU combined with IFN α can inhibit cell proliferation and promote cell death or apoptotic cell death by regulating the expression levels of the genes relating to cell proliferation and apoptosis. The molecular mechanism of HU and IFN α synergistically acting on leukemic cells is further elucidated from the expression level of the related genes which control the balance of survival and death or apoptosis of the cells.

关 键 词：羟基脲 干扰素-Α 基因表达 慢性粒细胞性白血病 

分 类 号：R733.7[医药卫生—肿瘤]