Effects of arsenic trioxide on growth,apoptosis and cell cycle of NB4,K562,BV173,U937 and HL60 cell line in vitro

Objective:To investigate the in vitro effect of Arsenic trioxide(AS2O3)on K562,BV173,U937 and HL60 cell lines,and compare the change of cell growth,apoptosis and cell cycle with NB4 cell line.Method:Various concentrations of AS2O3 were added on the culture system on various time points.Cells were counted using typlan staining.Flow cytometry with Annexin-V/PI staining was used to detect the apoptotic rate and to analysis the cell cycle of leukemic cell lines.Result:AS2O3 obviously inhibited the growth and proliferation of these cell lines,which showed a dose and time dependent relationship between 2 and 10 μmol/L AS2O3 concentrations.After culturing with 5 μmol/L AS2O3 for 48 h,the apoptotic rates of K562,BV173,U937 and H-60 cell line were 14.6±2.5%,19.4±3.1%,13.8±3.6% and 18.2±4.0% respectively,the differences were significant when comparing with those of NB4(41.8±2.6%)(P0.01).After culturing with 5μmol/L AS2O3 for 24h,the cell cycle analysis of NB4 were mostly presented with sub-G1 elevation(5.2% vs 3.2%),while of BV173,G0/G1 ratio were raised(55.2% vs 71.7%).The increase of G2/M ratio of K562 and U937 cell line were the most significant(22.6% vs 45.8% and 15.7% vs 48.6%,respectively).Conclusion:AS2O3 can greatly inhibit cell growth of these leukemic cell lines,but the mechanisms were quite different.The growth were inhibited by AS2O3 on NB4 cell line mostly via inducing apoptosis,while on K562,BV173 and U937 cell line,mostly via inducing cell cycle arrest.The cell cycle arrest and apoptotic insufficiency may be the probable mechanisms of AS2O3 resistance of K562,BV173 and U937 cell lines.