Fig. 2

 A combination of PI3K and mTOR inhibitors presented synergistic effects in limiting the survival of SCLC cells with high p-AKT. A Concentration-response cell survival curves of SCLC cell lines treated using BAY 80-6946. B Western blot analysis showing the expression of proteins involved in the PI3K/AKT/mTOR pathway in NCI-H446 cells treated with indicated concentrations of GSK2126458 (GSK), BAY 80-6946 (BAY), CAL-101 (CAL), BYL719 (BYL), RAD001 (RAD), or MK-2206 (MK) for 24 h. Levels of p-AKT(T308) and p-AKT(S473) were quantified and listed below the profiles. C Dose matrix of RAD001 in combination with BYL719 or MK-2206. Percent growth inhibition at each dose was assessed at 72 h after drug treatment (see left panel). Synergy distribution and synergy scores based on a zero interaction potency (ZIP) model (shown on the right). D List of ZIP scores presenting synergy of drug combinations (any two of CAL, BYL, RAD and MK) to the survival of NCI-H446 cells. E Western blot analysis showing the expression of the indicated proteins in NCI-H446 cells following single or combination treatment using GSK, BAY, CAL, BYL, RAD001, or MK-2206 at a concentration of 1.0 µM. The lower band under full-length RICTOR is cleaved RICTOR (c-RICTOR). The expression of c-PARP1 used to denote cell apoptosis. Levels of c-PARP1, c-RICTOR, c-RPTOR, p-AKT(T308) and p-AKT(S473) were quantified and listed below the profiles