索拉菲尼诱导NB4细胞凋亡机制研究  

Mechanisms of Sorafenib Induced NB4 Cell Apoptosis

作　　者：张韵洁[1,2] 刘心[1] 宋艳萍[2] 李罡灿[2] 周奈岑 王浩[2] 王琦霞 谢佳[2] 李光[2] 任婧婧[2] 高飞[2] 张晓波[2] 戴进前[2] 王璐[2] 牟娇[2] 

机构地区：[1]西安交通大学医学院第一附属医院血液科,陕西西安710061 [2]西安市中心医院血液病研究所,陕西西安710003

出　　处：《中国实验血液学杂志》2015年第1期77-82,共6页Journal of Experimental Hematology

摘　　要：目的:研究索拉菲尼对急性早幼粒细胞白血病NB4细胞增殖、凋亡的影响及其机制。方法:用不同浓度的索拉菲尼(0、1.5、3、6和12μmol/L)干预NB4细胞后,用MTT法检测细胞的增殖变化,用流式细胞术检测细胞的凋亡变化;提取细胞总蛋白后用Western blot方法检测细胞中凋亡相关分子Caspase-3、Caspase-8和MCL-1蛋白表达情况;提取细胞mRNA后用RT-PCR检测细胞中凋亡相关分子Caspase-3、Caspase-8和MCL-1基因表达。结果:与对照组相比,不同浓度的索拉菲尼干预均能有效抑制NB4细胞增殖,诱导细胞凋亡,并呈现浓度依赖效应。索拉菲尼干预可以上调NB4细胞促凋亡信号分子Caspase-3和Caspase-8的表达,并下调抗凋亡分子MCL-1的表达。结论:索拉菲尼可以抑制急性早幼粒细胞白血病NB4细胞增殖,诱导细胞凋亡,其机制与通过诱导细胞调节凋亡信号通路分子的表达有关。Objective：To investigate the effects of sorafenib on human acute promyelocytic leukemia cell NB4 and its mechanism. Methods：The human acute promyelocytic leukemia cell NB4 was treated with different concentrations （0、1.5、3、6 and 12μmol/L） of sorafenib, the proliferation inhibitory rate of NB4 cells was assayed by MTT, the apoptosis of NB4 was determined with flow-cytomatry after treatment; after extraction of total protein, the Western blot was performed to determine the expressions of apoptosis-relatived molecules Caspase-3, Caspase-8 and MCL-1. The mRNA expressions of Caspase-3, Caspase-8 and MCL-1 were determined by RT-PCR. Results： As compared with the control group, the proliferation of NB4 significantly decreased after treatment with different concentrations of sorafenib. The sorafenib significantly induced the apopotosis of NB4 cells in time- and dose-dependent manners. Furthermore, sorafenib treatment resulted in the obvious increase of the Caspase-3 and Caspase-8 protein and mRNA expressions, and down-regulated the MCL-1 protein and mRNA expressions in NB4 cells. Conclusion：Sorafenib can inhibit proliferation and induce apopotosis of human acute promyelocytic leukemia cell NB4 through the expression of Caspase-3 and Caspase-8, and down-regulation of the expression of MCL-1.

关 键 词：索拉菲尼 急性早幼粒细胞白血病 细胞增殖 细胞凋亡 CASPASE 

分 类 号：R733.71[医药卫生—肿瘤]