干扰素联合全反式维A酸逆转NB4-R1细胞的耐药机制研究

李美芳; 王海英; 冯安华; 马晓环; 杨敏

doi:10.13201/j.issn.1004-2806.2017.07.011

干扰素联合全反式维A酸逆转NB4-R1细胞的耐药机制研究

- 1. 潍坊医学院临床医学院(山东潍坊, 261000);
- 2. 潍坊医学院附属医院血液内科;
- 3. 泰山医学院临床医学院

详细信息

通讯作者: 王海英,E-mail:weiyifuyuan@sina.com

中图分类号: R773.71

收稿日期: 2016-10-14

Effect of interferon combined with ATRA on differentiation of ATRA resistant NB4-R1 cells

- 1. Clinical Medicine College, Weifang Medical University, Weifang, 261000, China;
- 2. Department of Hematology, Affiliated Hospital of Weifang Medical University;
- 3. Clinical Medicine College, Affiliated Hospital of Taishan Medical University

More Information

Corresponding author: WANG Haiying, E-mail: weiyifuyuan@sina.com

Received Date: 14 October 2016

摘要

摘要: 目的:探讨干扰素(IFN)联合全反式维A酸(ATRA)逆转维甲酸耐药急性早幼粒细胞白血病(APL)的机制。方法:取指数生长期的NB4-R1细胞分为6组,分别加入ATRA、IFN-α、IFN-γ、IFN-α+ATRA、IFN-γ+ATRA(其中ATRA终浓度为2 μmol/L,IFN-α和IFN-γ终浓度均为1000 IU/ml),以及不加药组的空白对照组,用MTT法检测细胞的增殖状况;蛋白免疫印迹试验测定各组NB4-R1细胞2 h IRF-1蛋白表达,以及IFN-α+ATRA组、IFN-γ+ATRA组诱导NB4-R1细胞观察8 h IRF-1蛋白表达的差异。结果:除ATRA组外,另外4个实验组均对NB4-R1细胞增殖有抑制作用,且联合用药的效果明显高于单独用药;5个实验组IRF-1蛋白均有表达,IFN-α+ATRA组、IFN-γ+ATRA组明显高于其他3组;IFN-α+ATRA组和IFN-γ+ATRA组比较,2 h内前者IRF-1蛋白表达量逐渐下降,而后者则无明显变化;至用药8 h后,IFN-α+ATRA组IRF-1蛋白表达基本消失,而IFN-γ+ATRA组的表达量仍较前无明显变化。结论:ATRA联合2种干扰素诱导NB4-R1细胞分化均有作用,但ATRA+IFN-γ效果更加显著;而IFN-α+ATRA组与IFN-γ+ATRA组比较,前者作用维持时间更长,可能与IRF-1蛋白持续表达有关。
- 全反式维A酸 /
- 干扰素 /
- 白血病,早幼粒细胞,急性 /
- IRF-1蛋白 /
- NB4-R1细胞株
Abstract: Objective:To investigate the mechanism of interferon (IFN) combined with all-trans retinoic acid (ATRA) in reversing retinoic acid-resistant acute promyelocytic leukemia (APL).Method:The experiment was divided into 6 groups,respectively ATRA,IFN-α,IFN-γ,IFN-α +ATRA and IFN-γ +ATRA( the final concentration of ATRA was 2 μmol/L,IFN-α and IFN-γ concentration was 1000 IU/m) and the blank control group without any drugs,cell proliferation was tested with MTT assay,Western Blot was used to determine the IRF-1 protein expression of NB4-R1 cells in 2 hours,IRF-1 protein expression of NB4-R1 cells in IFN-α+ATRA group,IFN-γ+ATRA group in 8 hours.Result:Except ATRA group,the other 4 experimental groups could inhibit the proliferation of NB4-R1 cells,and the combined treatment effect was significantly higher than that of single drug.The IRF-1 protein expressed in 5 experimental groups,and IFN-α+ATRA group,IFN-γ+ATRA group was significantly higher than those of the other 3 groups.The expression of IRF-1 protein in IFN-α+ATRA group decreased gradually within 2 hours,while IFN-γ+ATRA group had no obvious change.Eight hours after the treatment,expression of IRF-1 protein in IFN-α+ATRA group disappeared,whereas IFN-γ+ATRA group still had no obvious change.Conclusion:ATRA combined with either kind of interferon plays a role in inducing NB4-R1 cell differentiation,but ATRA+IFN-γ has more significant effects. The effect of IFN-α+ATRA group has longer duration when compared with IFN-γ+ATRA group,and the expression of IRF-1 protein may be sustained.
- all-trans retinoic acid /
- interferon /
- acute promyelocytic leukemia /
- IRF-1protein /
- NB4-R1cell

HTML全文

参考文献(7)

[1]	姜国胜,唐天华,毕可红.急性早幼粒细胞白血病对全反式维甲酸耐药的机制及其逆转[J].中华肿瘤杂志,2010,22(2):154-157.
[2]	楼叶江,潘晓蓉,许桂平,等.自分泌干扰素α在全反式维甲酸诱导RIG-G基因表达中的作用[J].中华医学杂志,2012,92(2):124-127.
[3]	He P,Liu Y,Zhang M.Interferon-γ enhances promyelocytic leukemia protein expression in acute promyelocytic cells and cooperates with all-trans retinoic acid to induce maturation of NB4 and NB4-R1 cells[J].Exp Ther Med,2012,3:776-780.
[4]	潘晓蓉,楼叶江,张长林,等.全反式维甲酸诱导RIG-g基因表达的调控机制研究[J].中国实验血液学杂志,2010,18(1):31-35.
[5]	柴晔,张连生,张玉芳.环孢素A与干扰素联合逆转复发难治性急性白血病多药耐药或难治性的临床研究[J].临床血液学杂志,2013,16(5):211-213.
[6]	Tanaka N,Ishihara M,Kitagawa M.Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1[J].Cell,2011,37:1825-1829.
[7]	刘宏涌,蒋敏,彭荷玲.柔红霉素对人急性早幼粒细胞白血病细胞株HL-60细胞及干扰素调节因子1、8、9表达的影响[J].内科,2014,9(2):124-127.[ZK)]