Vorinostat Synergism With PI3K Inhibitor NVP-BEZ235 Induces Apoptosis In Jurkat Cells

Objective To investigate the effect of Vorinostat combined with PI3 K inhibitor NVP-BEZ235 on T lymphocyte proliferation and its mechanism.Methods Human T-lymphocyte leukemia cell line Jurkat was cultured in vitro.After incubation with different concentrations of Vorinostat or(and)NVP-BEZ235,MTS was used to observe the effect of the two drugs alone or combined on cell proliferation,and the combined index of the two drugs was calculated.Studies,including flow cytometry to detect apoptosis;Western blot to detect PI3 K / Akt and FOXO3 a phosphorylation;immunoassay to detect FOXO3 a nuclear translocation;Western blot to detect the expression of Bim1.Finally,RNA interference Bim1 was used to observe the proliferation of Jurkat cells.Results: 1.0.12,0.24,0.36,0.48 and 0.6 μmol/L Vorinostat and 6,12,18,24,30nmol/L NVP-BEZ235 had synergistic effects on the growth and proliferation of Jurkat cells,in which the combination of Vorinostat and NVP-BEZ235 had a semiinhibitory concentration of 0.48 micromol/L and24 nmol/L,respectively;2.Vorinostat and/or NVP-BEZ235 can also promote the apoptosis of Jurkat cells.;3.Vorinostat or(and)NVP-BEZ235 could inhibit the phosphorylation of PI3K/Akt andFOXO3 a,induce FOXO3 a nuclear translocation and up-regulate the expression of Bim1.Silencing Bim1 could significantly reverse the inhibitory effect of Vorinostat and NVP-BEZ235 on Jurkat cell growth.Conclusion: 1.Vorinostat has synergistic effect on PI3 K inhibitor NVP-BEZ235 inhibiting Jurkat cell growth;2.Vorinostat can cooperate with NVP-BEZ235 to induce apoptosis of Jurkat cells.The mechanism is related to the influence of PI3K/Akt/FOXO3a/Bim1 pathway.