Figure 1. Development of acquired resistance to ALK inhibitors in the H3122 and H2228 cell lines.

(A) Cells were treated with the indicated doses of crizotinib or TAE684 for 72 h, and cell viability was then determined using the MTT assay. (B) Cells were treated with the indicated doses of crizotinib or TAE684 for 6 h. Molecules associated with ALK signaling activity were detected using Western blot analysis. Densitometry values were determined relative to the control after normalization to the non-phosphorylated form of each protein. (C) Lentiviral constructs containing the negative control (NT) and ALK shRNAs were introduced into parental or resistant cells, and ALK suppression was confirmed by Western blot analysis. Cell viability was measured by cell counting. **P < 0.001 compared with negative control shRNAs.