Fig. 6

Acquired resistance to ALK inhibition by ASP3026 is associated with upregulation of IGF-IR phosphorylation. a DEL and DEL-R (resistant to ASP3026) cells were treated for 5 days with increased concentrations of ASP3026, and cell viability was then determined. Treatment with ASP3026 was associated with significantly more reduction in the viability of DEL cells than the viability of the DEL-R cells. b Western blotting shows that the DEL-R cells have upregulated phosphorylation of NPM-ALK and IGF-IR. Changes in the basal levels of these proteins were not detected. β-Actin demonstrates equal protein loading. c Despite that the DEL-R cells demonstrated substantial resistance to ASP3026, PPP, at 72 h, decreased effectively the viability of these cells in a concentration-dependent manner. The results are shown as means ± SD of three independent experiments. d Treating the DEL-R cells with PPP was associated with substantial downregulation of IGF-IR, pIGF-IR, NPM-ALK, and pNPM-ALK. β-Actin supports equal protein loading