Crizotinib reduces Met phosphorylation and combined treatment with a new generation EGFR-TKI inhibits downstream pathways even in the presence of HGF.

<p>H1975 and H1975/HGF cells were incubated with crizotinib (300 nmol/L) and/or afatinib (300 nmol/L) (A, B) or WZ4002 (300 nmol/L) (C, D), for 1 hour. After stimulation with HGF (10 ng/mL) for 10 minutes, the cell lysates were harvested and the phosphorylation of indicated proteins was determined by western blot analysis. Each sample was assayed in triplicate, with each experiment repeated at least 3 times independently.