Author/Authors :
Jiang، نويسنده , , Xue-Jie and Huang، نويسنده , , Kai-Kai and Yang، نويسنده , , Mo and Qiao، نويسنده , , Liang and Wang، نويسنده , , Qiang and Ye، نويسنده , , Jie-Yu and Zhou، نويسنده , , Hong-Sheng and Yi، نويسنده , , Zheng-Shan and Wu، نويسنده , , Fu-Qun and Wang، نويسنده , , Zhixiang and Zhao، نويسنده , , Qing-Xia and Meng، نويسنده , , Fan-Yi، نويسنده ,
Abstract :
In this study, we investigated the synergistic effects of panobinostat and bortezomib on adriamycin-resistant HL60/ADR cells and refractory acute myelogenous leukemia (AML) primary cells. Combination of both agents had synergistic cytotoxicity on these cells, and increased the sensitivity of HL60/ADR cells to adriamycin. Panobinostat plus bortezomib was shown to modulate multiple apoptotic and drug metabolic related molecules, including activation of caspases, down-regulation of XIAP, Bcl-2 and MRP1. These effects were likely to be mediated via inhibition of AKT and NF-κB pathways. These findings provide evidence for clinic protocols using panobinostat and borezomib to overcome drug resistance in refractory AML patients.
Keywords :
bortezomib , Akt , NF-?B , leukemia , Panobinostat
