title: [Apoptosis of acute myeloid leukemia HL-60 cells induced by CDK inhibitor SNS-032 and its molecular mechanisms].
abstract: 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.
  
  
  
  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 JAK2/STAT3 pathway were detected by Western blotting.
  
  
  
  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-378c 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 STAT3 and protein expression of JAK2,C-MYC and MCL-1.
  
  
  
  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.
authors.affiliation: 1.Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; 2.Department of Hematology, Jiaxing Second People's Hospital, Jiaxing 314000, China.
authors.forename: Yan-xia
authors.initials: YX
authors.lastname: Han
authors.affiliation: Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
authors.forename: Liang-shun
authors.initials: LS
authors.lastname: You
authors.affiliation: Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Mao
authors.affiliation: Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
authors.forename: Xiu-jin
authors.initials: XJ
authors.lastname: Ye
authors.affiliation: Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
authors.forename: Wen-bin
authors.initials: WB
authors.lastname: Qian
mesh_terms: D017209:Apoptosis; D002470:Cell Survival; D015536:Down-Regulation; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D035683:MicroRNAs; C484864:N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide; D010080:Oxazoles; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013844:Thiazoles; C507924:JAK2 protein, human; D053614:Janus Kinase 2