姜黄素联合全反式维甲酸诱导耐药的急性早幼粒细胞白血病细胞分化的实验研究  

Effect of Curcumin Combined with ATRA on Differentiation of ATRA-resistant Acute Promyelocytic Leukemia Cells

作　　者：陈唐勇[1] 徐芬[2] 孔蕴源[1] 闻芳[1] 谢福源[1] 万腊根[1] 张长林[1] 

机构地区：[1]南昌大学第一附属医院检验科,江西南昌330006 [2]江西医学院上饶分院检验系,江西上饶334000

出　　处：《中国实验血液学杂志》2013年第4期895-898,共4页Journal of Experimental Hematology

基　　金：江西省教育厅科技计划项目青年基金(编号:GJJ10065);江西省卫生厅科技计划项目(编号:20091046);南昌大学科技计划项目(编号:2010-48)

摘　　要：本研究旨在探讨姜黄素联合全反式维甲酸(ATRA)对耐药的急性早幼粒细胞白血病细胞分化的影响及其分子机制。以耐药的NB4-R1细胞为实验对象,对细胞进行计数和细胞形态学观察,应用流式细胞术(FCM)检测姜黄素单用或联合ATRA对NB4-R1细胞增殖、分化的影响;用Western blot检测AKT磷酸化在细胞分化中的变化。结果显示,全反式维甲酸对NB4-R1细胞增殖无影响,但可增强姜黄素对NB4-R1生长的抑制作用。单用姜黄素或全反式维甲酸对细胞分化无影响,姜黄素联合全反式维甲酸可明显诱导细胞CD11b表达,细胞在形态上呈明显分化特征。全反式维甲酸可在短时间内促进NB4细胞AKT第473苏氨酸磷酸化,而对NB4-R1细胞中的AKT磷酸化影响不大。姜黄素可以促进NB4-R1细胞AKT磷酸化,而联合全反式维甲酸可进一步增强AKT磷酸化。结论:PI3K/AKT通路失活可能是导致APL细胞耐药的因素之一,而姜黄素通过活化PI3K/AKT信号通路逆转APL耐药,促进NB4-R1细胞分化。In order to investigate the effect of curcumin combined with all-trans retinoid acid （ ATRA ） on differentiation of ATRA-resistant acute promyelocytic leukemia （ APL） cells and its molecular mechanism,the NB4-R1, an ATRA-resistant APL cells,w as used as a model,counting of NB4-R1 and cell morphologic observation w ere performed,the effect of curcumin alone or combined w ith ATRA on proliferation,differentiation of NB4-R1 cells w as detected by flow cytometry （ FCM ） ,the change of AKT phophorylation in cell differentiation w as detected by Western blot. The results show ed that ATRA had no influence on NB4-R1 cell proliferation,but enhanced the inhibitory effect of curcumin on NB4-R1 cell grow th; the curcumin or ATRA alone did not affect NB4-R1 differentiation; curcumin combined w ith ATRA could obviously induce CD11b expression; the cell morphology show ed obvious differentiation chasacteristics. ATRA could promote phosphorylation of AKT in NB4 cells at short time,but not had effect on phosphorylation of AKT in NB4-R1 cells; the curcumin could enhance the phosphorylation of AKT in NB4-1R cells,the curcumin combined w ith ATRA could further enhance the phosphorylation of AKT. It is concluded that PI3K / AKT pathw ay inactivation may be one of the factors of drug resistance in APL and curcumin promotes differentiation of NB4R1 through activating PI3K / AKT pathw ay.

关 键 词：姜黄素 急性早幼粒细胞白血病 维甲酸耐药 细胞分化 

分 类 号：R733.71[医药卫生—肿瘤] R979.1[医药卫生—临床医学]