2-甲氧基雌二醇对白血病K562细胞凋亡相关基因表达的影响及其机制  

Effects and mechanisms of 2-methoxyestradiol on the expression of apoptosis-related genes in K562 leukemia cells

作　　者：李栋梁[1] 张静[2] 潘崚[3] 侯兰芬[1] 王志伟[1] 郭晓[1] 

机构地区：[1]解放军白求恩国际和平医院血液科,石家庄050082 [2]河北以岭医院内科 [3]河北医科大学第二医院血液科

出　　处：《白血病．淋巴瘤》2009年第6期323-326,330,共5页Journal of Leukemia & Lymphoma

基　　金：基金项目：河北省科学技术研究与发展指导计划项目（072761183）

摘　　要：目的探讨2-甲氧基雌二醇（2-ME）对白血病K562细胞凋亡的影响及其作用机制。方法实验分为3组，对照组：培养基中不含2-ME；实验组：分别用1、2、4、8、16μmol／L的2-ME处理K562细胞36h后观察各项指标的变化；阴性对照组：培养液中以无RNase蒸馏水代替K562细胞。应用原位细胞凋亡法（TUNEL）、流式细胞术（FCM）、半定量IT—PCR及黄嘌呤氧化酶法分别检测K562细胞凋亡率、Caspase-3、性连锁凋亡抑制蛋白（XIAP）及其基因表达、超氧化物歧化酶（SOD）与活性氧（ROS）水平。结果不同浓度的2-ME与K562细胞作用36h后，2-ME在-定的浓度范围内以剂量依赖形式诱导K562细胞凋亡；2-ME通过上调促凋亡因子Caspase-3和（或）下调抗凋亡因子XIAP的表达，降低SOD及增加ROS水平等途径促进K562细胞凋亡，这可能是2-ME诱导K562细胞凋亡的机制之-。结论2-ME能够以剂量依赖形式诱导K562细胞凋亡，显示了其在慢性粒细胞白血病（CML）治疗中的潜在价值。Objective To investigate the effects of 2-methoxyestradiol（2-ME） on apoptosis of K562 cells and its mechanisms. Methods The K562 cells were cultured and divided into three groups. The control group： K562 cells were cultured without 2-ME treatment. The experimental group： K562 cells were cultured in the medium containing different concentrations of 2-ME （1, 2, 4, 8 and 16 txmol/L） for 36 h. The negative control group： K562 cells were replaced by water without RNase in the medium containing different concentrations of 2-ME for 36 h. The apoptosis rate, the protein and its mRNA expression of Caspase-3 and XIAP, the activity of superoxide dismutase （SOD） and reactive oxygen species （ROS） of K562 cells was detected by TUNEL, flow cytometry （FCM）, half-quantitative RT-PCR and xanthenes oxidized enzyme assay, respectively. Results After treated with 2-ME at different concentrations for 36 hours, in the specified concentration range, 2-ME induced apoptosis of K562 cells in a concentration-dependent manner. The possible functional mechanism of 2-ME was to up-regulate Caspase-3 but down-regulate XIAP mRNA expression, and increase ROS activity but decrease SOD activity. Conclusion 2-ME can induce apoptosis of K562 cells in a concentration-dependent manner and indicate its promising potential in the treatment of chronic myeloid lcukemia（CML） patients.

关 键 词：K562细胞 2-甲氧基雌二醇 凋亡 白血病 髓样 慢性 

分 类 号：R733[医药卫生—肿瘤]