Fig. 1

SCLC cell lines with high p-AKT were sensitive to PI3K/mTOR dual inhibition. AÂ Western blot analysis showing the expression of proteins involved in the PI3K/AKT/mTOR pathway in 13 SCLC cell lines. BÂ Concentration-response cell survival curves of SCLC cell lines treated using GSK2126458. CÂ Correlation between survival response (IC50) and the levels of p-AKT(T308), p-AKT(S473), PIK3CA, PTEN, p-P70S6K, and p-4EBP1. Symbols of the cell lines are the same as those denoted in B. R2, coefficient of determination. DÂ Tumor growth curve of xenografted NCI-H446 cells in nude mice. Mice were orally (PO) administered with vehicle (10 ml/kg) or GSK2126458 (1.5Â mg/kg) when the tumor size reached approximately 200 mm3 using a 5-on-2-off cycle for 2 consecutive weeks. EÂ Western blot analysis results showing the expression of AKT, p-AKT(T308), p-AKT(S473), cleaved PARP-1 (c-PARP1), and a GAPDH loading control in xenografted NCI-H446 tumors in mice oral administered with GSK2126458 (3.0Â mg/kg). Tumors were harvested at 2, 6, and 24Â h after drug treatment