伊马替尼联合槲皮素对K562细胞增殖和凋亡协同作用的机制研究  

Synergistic effect on inhibition of proliferation and induction of apoptosis by imatinib combined with quercetin in K562 cell line

作　　者：游建华[1] 周励[1] 杜圣红[2] 陈娟[2] 贾培敏[2] 童建华[3] 吴文[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院血液科,上海200025 [2]上海交通大学医学院附属瑞金医院上海血液学研究所,上海200025 [3]上海交通大学医学院附属瑞金医院检验系,上海200025

出　　处：《内科理论与实践》2015年第4期300-304,共5页Journal of Internal Medicine Concepts & Practice

基　　金：国家自然科学基金项目(项目编号:81170508;81470317)

摘　　要：目的:探讨槲皮素联合伊马替尼对K562细胞增殖的影响以及诱导凋亡的机制。方法:将不同浓度的槲皮素、伊马替尼单药和联合用药作用于K562细胞,绘制协同曲线。将0.25μmol/L伊马替尼与25μmol/L的槲皮素联合作用于K562细胞,通过细胞计数检测细胞增殖,流式细胞术检测细胞周期、线粒体跨膜电位的变化,蛋白质印迹法检测相关蛋白的表达。结果:0.25μmol/L伊马替尼联合25μmol/L槲皮素对K562细胞有明显的协同抑制生长和诱导凋亡作用。两药联合处理能降低K562细胞线粒体跨膜电位,使胱天蛋白酶(caspase)9和胱天蛋白酶3发生剪切,并明显下调B细胞淋巴瘤(Bcl)2样蛋白1(Bcl-xl)和髓样细胞白血病-1(Mcl-1)蛋白的表达。结论:伊马替尼与槲皮素协同抑制K562细胞生长并诱导细胞凋亡,其机制主要通过下调Bcl-xl以及Mcl-1蛋白的表达,从而激活线粒体凋亡途径来实现的。Objective To study the synergistic effect of imatinib combined with quercetin on proliferation and apop- tosis in K562 ceils. Methods K562 cells were treated with quercetin or imatinib by different concentration alone or in combination. Cell proliferation was assessed by cell count. Distribution of cell cycle and change of mitochondrial mem- brane potential were measured by flow cytometry. Caspases, B cell lymphoma （Bcl）-xland myeloid cell leukemia（Mcl）-I expressions were detected by Western blotting. Results The combination of imatinib（0.25 μmol/L） and quercetin（25 μmol/ L） showed significant synergistic effect on proliferation inhibition and apoptosis induction in K562 cells, which might be due to decrease of mitochondrial membrane potential, cleavage of capase-9 and capase-3, and down-regulation of Bcl-xl and Mcl-1 expression. Conclusions The synergistic effect on proliferation inhibition and apoptosis induction by the combi- nation of imatinib and quereetin in K562 cell line is possibly through down-regulation of Bcl-xl and Mcl-1 expression, and activation of mitochondrial signaling pathway.

关 键 词：伊马替尼 槲皮素 K562细胞 增殖 凋亡 

分 类 号：R733.72[医药卫生—肿瘤]