Figure 4

Treatment with Sorafenib inhibits the Ras/Raf/Erk and PI3K/Akt/mTOR pathway. Western blot experiments for serveral target proteins are displayed. ALL cell lines were treated with Sorafenib for the indicated time periods. Total cell lysates (25 μg) were separated by electrophoresis on an 8% SDS-Page gel. Membranes were incubated with the indicated antibodies against Erk1/2 and PI3K/AKT/mTOR signaling pathway-related proteins. GAPDH was used as control for equal loading. (A) Sorafenib induced down-regulation of pErk1/2 (Thr202 and Thr204) in SEM cells at 4 h and 24 h after treatment. (B) Inhibition of mTOR was detectable as a decrease of p-4EBP-1 (Thr70 and Ser65) protein in B- and T-ALL cells with 7.3 μM Sorafenib. (C) Sorafenib down-regulated the phosphorylation of Akt (Thr308 and Ser473) and reduced the phosphorylation of FoxO3A (Thr32) in SEM, RS4;11 and Jurkat cells.