17-AAG Induces Apoptosis Of K562, HL-60 Cells And Effects The Growth With Chemotherapeutics

Objective:To investigate the growth inhibition and apoptosis of K562 and HL-60 cells exposured to the heat shock protein 90 inhibitor 17-AAG alone or combined with ch -emotherapeutics respectively.To study the role of Hsp90 inhibitor and therapeutic alliance in the treatment of leukemia.Methods:The MTT assay was used to quantify the growth inhibition of K562 and HL-60 cells after exposure to 17-AAG,The apoptosis rates of cells were measured by Annexin V-FITC staining method and flow cytometry(FCM),Hoechst 33258 staining method was used to observe the cell's morphologic changes.After exposure to 17-AAG, Cytorabine or epirudicin alone or combinations,the effects of drugs combinations were analyzed by using the median-effect method of Chou and Talalay.Results:(1) 17-AAG could inhibit the growth of K562 and HL-60 cells and induce their apoptosis in time and dose-dependently.(2) 17-AAG inhibited K562 and HL-60 cells growth with the ICS0 of 0.664±0.003μmmol/L and 1.246±0.032μmol/L.(3)17-AAG, cytorabine or epirudicin alone or two drug combinations could inhibit the growth of K562 and HL-60 cells in a dose- and time-dependent manner.(4) The effects of combined use of 17-AAG with Cytorabine or epirudicin were antagonistic at lower concentration,and synergistic at higher concentration.(5) The ratio of drug concentration can influence the combination index(CI).Conclusion:As a new antitumor agent,the heat shock protein 90 inhibitor 17-AAG could inhibit the proliferation and induce the apoptosis of human leukemia cells K562 and HL-60 cells effectively,which combined with epirudicin could display synergistic activity.The ratio of drug concentration is a significant factor that can effect on the growth inhibition.