三氧化二砷诱导白血病细胞凋亡与核因子-κB活化的关系  

Arsenic Trioxide Induced Leukemic Cell Apoptosis Relative to NF-κB Activation

作　　者：许小平[1] 许晓巍[1] 易克[1] 陈莉[1] 陈少谊[1] 周芳[1] 李倩玉[2] 

机构地区：[1]第二军医大学长海医院血液科,上海200433 [2]第二军医大学东方肝胆外科医院病理科,上海200433

出　　处：《中国实验血液学杂志》2005年第5期764-768,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金资助项目;编号39770330

摘　　要：为了研究三氧化二砷(As2O3)诱导白血病细胞凋亡与核因子-κB(NF-κB)活化以及血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP9)表达的关系,应用流式细胞仪AnnexinVFITC法检测白血病细胞系K562n凋亡;采用免疫组织化学方法半定量分析K562n细胞NFκB、VEGF、MMP9表达的动态变化。结果显示:As2O3在诱导K562n细胞凋亡的过程中可活化NFκB,而VEGF、MMP9的表达也随之增强。地塞米松(DXM)1μmol/L能显著增加As2O3诱导K562n细胞凋亡的作用和抑制K562n细胞NFκB活化,细胞凋亡增加率为43.04%,(P<0.05),NFκB活化抑制率为31.15%(P<0.05),VEGF、MMP9变化与NFκB一致。结论:As2O3诱导K562n细胞凋亡的过程中可使NFκB活化,VEGF、MMP9表达亦随之增强;DXM可通过抑制NFκB活化增强其诱导K562n细胞凋亡的作用,VEGF、MMP9的表达也随之下降。To investigate the relationship of As2O3-induced leukemic cell apoptosis with NF-κB activation and expression of VEGF, MMP9, apoptosis of K562-n cells induced by As2O3 was analyzed by Annexin V, the dynamic changes of NF-κB, MMP9 and VEGF expressions were detected by immunohistochemistry. The results showed that activity of NF-κB could be increased, accompanied by higher level of expression of MMP9 and VEGF when apoptosis of K562-n cells was induced by As：O3. Dexamethasome not only increased significantly the apoptotic rate, but also suppressed the activation of NF-~B of K562-n cells induced by As2O3. Furthermore, there was a positive correlation between the expression of MMP9,VEGF and the activity of NF-κB. It is concluded that As2O3 can induce apoptosis, in the meanwhile, activate NF-κB and up-regulate exPression of MMP9 and VEGF in K562-n cell line. The mechanism of apoptosis of K562-n cells enhanced by dexamethasome may be related to suppression of the activation of NF-κB and expression of MMP9 and VEGF.

关 键 词：三氧化二砷 核因子-ΚB 血管内皮生长因子 基质金属蛋白酶 细胞凋亡 白血病 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]