Combination of triciribine and p38 inhibitors enhances the differentiation effect on myeloid leukemia cells

Differentiation therapy with all-trans retinoic acid (ATRA) is well established for acute promyelocytic leukemia (APL). However, the narrow application and tolerance development of ATRA remain to be improved. A number of kinase inhibitors have been reported to induce differentiation. In this study, we challenged several combinations of these kinase inhibitors. As a result, we found that the combination of Akt inhibitor Triciribine (TCN) and several p38 MAPK inhibitors have profound effect for differentiation in several myeloid cell lines. To reveal the molecular mechanisms involved in TCN and p38 MAPK inhibitor induced differentiation, we performed microarray analysis. We use 4 samples. As a control, we used DMSO sample. The other samples are Triciribine (TCN), PD169316 and TCN+PD169316. All samples were exposed to reagents for 72 hours.