Figure 4.

PIK-75 inhibits PI3K-AKT activity and overcomes acquired venetoclax resistance in vitro and in vivo. (A) Rec-1 and Rec1-Re cells were treated with 50 nM PIK-75 for 24 h and subjected to RPPA analysis. A heatmap was made with NormLog2_MedianCentered values that were < and >0.5 times between untreated and treated samples. (B, C) Rec-1 and Rec1-Re cells were treated with designated venetoclax or PIK-75 concentrations for 24 h. Cells were harvested and analyzed by western blotting (B) and cell apoptosis assay (C) to confirm the RPPA data and biological effects. (D-F) 5×10⁶ Rec1-Re cells were injected subcutaneously into each NSG mouse and treated with vehicle, 50 mg/kg venetoclax, or 10 mg/kg PIK-75, daily. Tumor volumes were measured weekly (D), and mouse blood was collected weekly; human B2M in mouse serum was measured by ELISA assay (F). Tumor weight was measured at the end of experiment (E). Student t test was used for statistical analysis, n=5.