U0126增强索拉非尼对K562细胞增殖抑制、凋亡及诱导分化作用  

U0126 enhances sorafenib-induced proliferation inhibition,apoptosis and differentiation in K562 cells

作　　者：陈琰[1,2] 肖若芝[1,2] 王立琳[1,2] 何程明[1] 阮星星[1] 熊慕珺[1,2] 林东军[1,2] 

机构地区：[1]中山大学附属第三医院血液科,广东广州510630 [2]中山大学血液病研究所,广东广州510630

出　　处：《中国病理生理杂志》2011年第5期859-864,共6页Chinese Journal of Pathophysiology

基　　金：广东省科技计划资助项目(No.2006B35501008)

摘　　要：目的:观察索拉非尼、索拉非尼联合MEK激酶抑制剂U0126对人慢性粒细胞白血病K562细胞株增殖、凋亡及分化的影响,并初步探讨其机制。方法:CCK-8法观察索拉非尼、U0126单用及不同浓度索拉非尼联合10μmol/L U0126作用K562细胞48 h后细胞增殖活力变化;PI单染法及Hoechst 33342染色法观察索拉非尼、U0126单用及索拉非尼联合U0126对K562细胞株的凋亡诱导作用;细胞周期分析及联苯胺染色观察索拉非尼、U0126单用及低浓度索拉非尼联合U0126是否诱导K562细胞株向红系分化;采用免疫印迹法检测c-Myc蛋白表达。结果:MEK抑制剂U0126增强了索拉非尼对K562细胞增殖抑制、促凋亡及诱导分化作用。两药联用显著下调K562细胞c-Myc蛋白水平。结论:MEK抑制剂U0126增强索拉非尼对K562细胞增殖抑制、凋亡及诱导分化作用,这可能与其协同下调c-Myc蛋白有关。AIM： To observe the effects of sorafenib and sorafenib combined with an MEK kinase inhibitor U0126 on the proliferation,apoptosis and differentiation in human chronic myelogenous leukemia cell line K562.METHODS： K562 cells were treated with different concentrations of sorafenib and U0126 or 10 μmol/L U0126 combined with different concentrations of sorafenib for 48 h.Cell inhibitory rate was determined by CCK-8 assay.Apoptosis analysis was conducted by Hoechst 33342 and PI staining.Cell cycle analysis and benzidine staining were used to confirm K562 cells towards erythroid differentiation.The protein expression of c-Myc was detected by Western blotting.RESULTS： U0126 enhanced sorafenib-induced proliferation inhibition,apoptosis and differentiation in K562 cells.Sorafenib combined with U0126 remarkably reduced the protein level of c-Myc.CONCLUSION： U0126 synergistically enhances sorafenib-induced proliferation inhibition,apoptosis and differentiation in K562 cells through reducing c-Myc protein level.

关 键 词：索拉非尼 U0126 K562细胞 细胞凋亡 c-Myc 

分 类 号：R733.7[医药卫生—肿瘤]