Fig. 3

GSK2126458 induces proteolytic cleavages of RICTOR and RPTOR in SCLCs with high p-AKT. A Western blot analysis showing the time-dependent cleavages of RICTOR and RPTOR in NCI-H446 cells treated using GSK2126458 (625 nM). The expression level of p-AKT(S473) is shown to illustrate the efficacy of GSK2126458 in inhibiting AKT phosphorylation. The black stars denote full-length RICTOR/RPTOR, and the red arrowheads indicate cleaved RICTOR/RPTOR. Levels of c-RICTOR and c-RPTOR were quantified and listed below the profiles. B Western blot analysis illustrating the expression of AKT, p-AKT(S473), RICTOR, and RPTOR in SCLC cell lines treated using GSK2126458 at indicated concentrations for 24 h. The black stars denote full-length RICTOR/RPTOR, and the red arrowheads indicate cleaved RICTOR/RPTOR. C Correlation between the level of p-AKT(S473) normalized to GAPDH and the ratio of c-RICTOR in eight SCLC cell lines treated as described in (A). D Correlation between the survival response (i.e., IC₅₀) of GSK2126458 and the ratio of c-RICTOR in SCLC cell lines. The coefficient of determination (R²) in each curve was calculated and presented in the figure