title: [Effect of valproic acid on the expression of P27(Kip1) and P170 and drug resistance of HL-60/HT cells].
abstract: OBJECTIVE
  To investigate the effect of valproic acid on the expression of P27(Kip1) and P170 and drug resistance of leukemia HL60/HT cell line and explore its possible mechanisms.
  
  
  METHODS
  HL-60/HT cells were derived from HL-60 cells induced by harringtonine (HT) in gradient concentrations. The inhibitory effect of valproic acid on the proliferation of HL-60 and HL-60/HT cells was evaluated by MTT assay, and the P27(Kip1) expression, P170 expression and cell cycle of the cells were analyzed with flow cytometry.
  
  
  RESULTS
  The multidrug-resistant HL-60/HT was acquired, which showed a stable drug-resistant index with increased IC(50) of HT, VCR, DNR and Ara-c by 9.30, 5.20, 4.91 and 3.65 folds, respectively, as compared with those of HL60 cells. The expression of P27(Kip1) in HL-60/HT cells was significantly lower but P170 expression significantly higher than that of HL-60 cells and normal mononuclear cells (P<0.05). The expressions of P27(Kip1) and P170 showed no significant difference between normal mononuclear cells and HL-60 cells. The growth inhibition rate of VPA combined with Ara-C was significantly higher than that of valproic acid or Ara-C alone in HL-60/HT cells and HL-60 cells (q=1.37 and 1.51, respectively). HL-60/HT and HL-60 cells cultured in the presence of VPA resulted in a significant increase in the expression of P27(Kip1) and the G(1)-phase cells (P<0.05), but the expression of P170 underwent no significant changes (P>0.05).
  
  
  CONCLUSIONS
  HL-60/HT cells have lower P27(Kip1) expression compared with HL-60 cells. Valproic acid can inhibit the growth of HL-60/HT cells and enhance their Ara-C sensitivity possibly by increasing P27(Kip1) expression and causing cell cycle arrest in G(1) phase.
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. sumliyiqing@163.com
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Li
authors.forename: Song-Mei
authors.initials: SM
authors.lastname: Yin
authors.forename: Shuang-Feng
authors.initials: SF
authors.lastname: Xie
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ma
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Nie
authors.forename: Xiu-Ju
authors.initials: XJ
authors.lastname: Wang
authors.forename: Yu-Dan
authors.initials: YD
authors.lastname: Wu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents / Q000494:pharmacology*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D003561:Cytarabine / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; C436291:CDKN1B protein, human; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D003561:Cytarabine; D050760:Cyclin-Dependent Kinase Inhibitor p27; D014635:Valproic Acid