Empirical Study on the Mechanism of the Apoptosis Induced by VPA

Objective The aim of this survey is to investigate the mechanism of VPA inducing the apotosis of leukemic cells on the molecular level.Methods The leukemic cell lines U937 were divided into three groups (control group;1 mmol/L VPA group and 1 mmol/L VPA+1 μmol/L zVAD-fmk group).72 hours after treated,cells were double stained with Annixin-ⅴand PI,then was analyzed with the FCM to detect apoptosis.Before and after treated the mean fluorescent index (MFI) of Bcl-2、Bax 、Bcl-xl and the levels of caspase3、8、9 in cells were also detected with the FCM.Results 1mmol/L VPA induced the apoptosis of U937,the apoptotic rate of U937 was(75.78±4.20)%.Compared with the control group there were significant difference (P0.01);Pan-caspase inhibitor zVAD-fmk could fully inhibit the apoptosis of U937,and the apoptotic rate was(2.89±0.36)%(P0.01).The MFI of Bcl-2、Bax and Bcl-xl in the cell line had not changed significantly(P0.05).After treated with VPA,the level of caspase 3 in U937 was from (14.09±1.19)% up to (32.30±2.47)%,and caspase 8 was from(4.58±1.41)% up to (86.47±3.26)%(both P0.01),but there was no significant change in caspase 9.Conclusion VPA induce the apoptosis of U937 through the activation of caspase 3 and 8; and it does these without the alteration of the expression of Bcl-2、Bax and Bcl-xl.