[Effect of valproic acid on the expression of P27(Kip1) and P170 and drug resistance of HL-60/HT cells].
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.
Li
Yi-Qing
YQ
Department of Hematology, Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. sumliyiqing@163.com
Yin
Song-Mei
SM
Xie
Shuang-Feng
SF
Ma
Li-Ping
LP
Nie
Da-Nian
DN
Wang
Xiu-Ju
XJ
Wu
Yu-Dan
YD
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*
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