Discovery of Novel AKT Inhibitors with Enhanced Anti-Tumor Effects in Combination with the MEK Inhibitor
Figure 2
Effect of GSK2110183 on AKT signaling and growth inhibition in human cancer cell lines.
A, BT474 (left) and LNCaP (right) cell lines were treated with DMSO or GSK2110183 for 1 h. Western analysis was performed to assay levels of phosphorylated and total GSK-3, PRAS40, AKT and ERK, phosphorylated Foxo, Caspase 9, and MEK. Tubulin was used as a loading control. B, Scatter plot of EC50's for anti-proliferative effect of GSK2110183 against various haematological cancer cell lines. Cell lines are grouped according to their disease classification and sub-divided into cellular origin of B cell (black diamond), pre-B cell (red diamond), T cell (blue diamond) or other (grey diamond). C, Scatter plot of EC50's for various solid cancer cell lines treated with GSK2110183. Cells were treated as described above. Cell lines are grouped by tissue of origin then further divided by genetic status. KRAS/BRAFV600E mutation status is represented by color with mutant (red), wild type (black) or other (blue); whereas PIK3CA or PTEN status represented with shape, mutant (diamond) and wild type (circle).