四嗪二甲酰胺对K562和K562/Adr的作用及其与NF-κB信号分子的关系  

Effect of ZGDHu-1 on Proliferation of K562 and K562/Adr and the Expression of NF-κB Protein

作　　者：张玉霞[1] 周永列[1] 徐菲[1] 邱莲女[1] 

机构地区：[1]浙江省人民医院检验中心,杭州310014

出　　处：《医学研究杂志》2011年第8期50-54,共5页Journal of Medical Research

基　　金：国家自然科学基金资助项目(30973568)

摘　　要：目的探讨四嗪二甲酰胺(ZGDHu-1)对慢性粒细胞白血病细胞株K562(K562-S)和耐药细胞株K562/Adr(K562-R)的抑制作用及其对p210 BCR/Ab l融合蛋白和转录核因子κB(NF-κB)表达的影响。方法 MTT比色法观察其对K562-S细胞增殖的抑制作用,采用Hoechst 33258荧光染色检测细胞凋亡,流式细胞仪及细胞克隆形成初步分析其对白血病干细胞的影响,通过Western印迹分析PARP-1、p210 BCR/Abl、c-Abl、NF-κB的表达。结果不同浓度的ZGDHu-1对K562-S细胞均有增殖抑制作用,呈现剂量-时间依赖关系,ZGDHu-1作用48h时的IC50值为0.25μg/ml。在ZGDHu-1作用7天后,K562-S及K562-R细胞克隆形成被完全抑制。ZGDHu-1作用48h后,出现PARP-1裂解,诱发细胞凋亡,下调K562-R细胞p210 BCR/Abl及c-Abl的表达,抑制K562-S及K562-R细胞质内NF-κB/p65的表达。结论 ZGDHu-1能够抑制K562-S及耐药细胞株K562/Adr(K562-R)细胞的增殖,促进细胞凋亡。通过抑制p210 BCR/Abl的表达,降低NF-κB的活性,阻断NF-κB信号传导通路,尤其对于耐药型白血病细胞具有广泛的应用价值。Objective To explore the effect of ZGDHu - 1 on proliferation of chronic myeloid leukemia cell K562（ K562 - S） and its multidrug resistant cell line K562/Adr（ K562 - R） , and to discuss the expression of the p210 BCR/Abl and NF - κB. Methods MTT was used to determine the proliferative effects of ZGDHu - 1 on K562 - S cell. K562 - S and K562 - R cell suspension was stained with Hoechst33342. The leukemia stem ceils was preliminary analyzed by flow eytometry and colon forming. Western blotting was used to examine the expression of the PARP - 1, p210 BCR/Abl and NF - κB. Results ZGDHu - 1 could inhibit K562 - S cell proliferation within different concentration,which be presented in dose and time dependent manner. Treated with ZGDHu -1 for 48 hours,the K562 -S cell IC50 value was 0. 25μg/ml. The K562 -S and K562 -R cells apoptosis was confirmed by Hoechst33258 straining. Treated with ZGDHu - 1 after 7 days,K562 - S and K562 - R cell colons forming was absolutely inhibited. After incubating with ZGDHu - 1 for 48 hours, the cleavage of PARP was observed in the process of apoptosis of K562 - S cell and K562 - R cell,and the protein expressions of p210BCR/ Abl,e - Abl and NF - KB/p65 were all decreased. Conclusion ZGDHu - 1 can inhibit K562 - S and K562 - R cell proliferation and induce apoptosis. The mechanism may be associated with inhibiting the expression of p210 BCR/Abl and the blockage of NF - κB signal transduction pathway. ZGDHu - 1 may have widespread application value in treatment of drug resistance to chemotherapy in the patients with leukemia.

关 键 词：慢性粒细胞性白血病BCR/Abl NF—κB凋亡 

分 类 号：R972[医药卫生—药品]