Apoptosis of acute myeloid leukemia HL-60 cells induced by CDK inhibitor SNS-032 and its molecular mechanisms
10.3785/j.issn.1008-9292.2015.03.009
- VernacularTitle:细胞周期蛋白依赖激酶抑制剂诱导HL-60细胞凋亡及分子机制研究
- Author:
Yan-Xia HAN
1
;
Liang-Shun YOU
;
Hui LIU
;
Li-Ping MAO
;
Xiu-Jin YE
;
Wen-Bin QIAN
Author Information
1. 浙江大学医学院附属第一医院血液科
- Keywords:
Leukemia,myeloid,acute;
MicroRNAs;
Cyclin-dependent kinases/biosynthesis;
Janus kinases;
STAT3 transcription factor;
Protein-tyrosine kinases/metabolism;
Signal transduction;
HL-60 cells;
Apoptosis;
Tumor cells,cultured
- From:
Journal of Zhejiang University. Medical sciences
2015;(2):174-178
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effects of cycle-dependent kinase ( CDK) inhibitor SNS-032 on apoptosis in human acute myeloid leukemia ( AML) HL-60 cells and its molecular mechanisms .Methods:Cultured AML HL-60 cells were treated with various concentrations of SNS-032 .Cell apoptosis was determined with flow cytometry;cell viability was measured by MTT assay; the profiles of microRNA expression of HL-60 cells were analyzed by microRNA microarray;the protein expressions of JAK 2/STAT3 pathway were detected by Western blotting .Results:Apoptosis of AML HL-60 cells was induced by SNS-032; the rate of apoptosis was (5.9 ±1.7)%, (12.1 ± 3.1)% and (59.4 ±3.6)% when HL-60 cells were treated with 0,100 and 200 nmol/L SNS-032.MicroRNA microarray analysis revealed that the levels of miR-30a, miR-183, miR-20b, miR-26b, miR-20a, miR-589, miR-107, miR-181a, miR-106a, miR-17 and miR-378 c were down-regulated by SNS-032 , whereas the levels of miR-320a and miR-H7* were up-regulated.Western blotting showed that SNS-032 strongly inhibited phosphorylation of STAT 3 and protein expression of JAK 2, C-MYC and MCL-1.Conclusion:CDK inhibitor SNS-032 can induce apoptosis of AML HL-60 cells, which is associated with the inhibition of MCL-1,C-MYC and JAK2/STAT3, and down-regulation of miR-17-92 family .
