Effect of LY294002 on Cell Cycle and Apoptosis of Multidrug Resistant HL60/VCR Cell Line

OBJECTIVE:To explore the effect of the specific inhibitor-LY294002 of the signaling pathway PI3K/AKT on cell cycle and apoptosis of HL60/VCR cells and its mechanism.METHODS:Vincristine(VCR) resistant HL60/VCR were treated with LY294002(final concentration at 1.0,2.5,5.0,or 10 μmol·L-1) or without LY294002(control).IC50 was detected by MTT;flow cytometry was used to evaluate apoptosis and cell cycle distribution,and changes of Bcl-2,CyclinD1 gene mRNA levels were detected by reverse transcription polymerase chain reaction.RESULTS:As compared with control,LY294002 significantly reduced the IC50 value in HL60/VCR to vincristine in a concentration dependent manner(P 0.05).LY294002 significantly increased the rate of apoptosis,arrested cells in G0/G1 phase and reduced the levels of Bcl-2 and CyclinD1 mRNA(all P0.05).CONCLUSION:The underlying mechanism for LY 294002 to promote apoptosis of HL60/VCR and suppress cell proliferation lies in its impact on Bcl-2 level and CycllinD1 gene expression.