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Fig. 5 | Molecular Cancer

Fig. 5

From: Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance

Fig. 5

Activation of antiapoptotic signaling through the Ack1/AKT pathway contributes to ASK120067 resistance. a The levels of AKT phosphorylation (p-AKT) in NCI-H1975 and 67R cells were determined by immunoblotting analysis. b The inhibitory activity of ASK120067 on p-AKT expression in NCI-H1975 cells and 67R cells was compared. c Knockdown of Ack1 expression using short hairpin RNA (shRNA) decreased the levels of phosphorylated AKT in 67R cells. d The mRNA and protein levels of proapoptotic protein BIM in NCI-H1975 and 67R cells were determined by real-time PCR (left panel) and Western blot analysis (right panel), respectively. e The effect of ASK120067 on BIM expression in NCI-H1975 and 67R cells was examined. f Knockdown of Ack1 expression in 67R cells increased the expression of BIM by decreasing the phosphorylation of AKT. g to i, the combination of ASK120067 with Ack1 inhibitors synergistically suppressed AKT activation g and induced the transcription h and protein expression of BIM i

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