Effect of saracatinib on the Src and PI3K signaling pathways. A, treatment with saracatinib (0.5 µmol/L) at 30 minutes, 1, 4, 8, and 24 hours resulted in a decrease in the phosphorylation of Src, FAK, and Stat-3 in the LS180 sensitive cell line (N = 3). Src inhibition also decreased the activation of PDK-1, AKT, and S6 and increased protein levels of p27kip1. B, co-immunoprecipitation (IP) of Src showed a decrease in binding to p85 at 0.5, 1, and 4 hours after treatment with saracatinib. Conversely, immunoprecipitation of p85 resulted in an increase in binding the p110-α subunit (N = 3). C, the activation of the PI3K pathway (Akt and S6) was decreased with saracatinib treatment in CRC040 (sensitive), CRC020 (resistant), and HT29 (resistant). CRC, colorectal cancer.