【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。更多还原

【Abstract】 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.更多还原