Skip to main content
Fig. 4 | Molecular Cancer

Fig. 4

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

Fig. 4

Activation of Ack1 is sufficient to cause resistance to ASK120067, and drug combinations suppress proliferation and induce apoptosis of ASK120067-resistant cells. a Immunoblot analysis of total Ack1 and phosphorylated Ack1 (p-Ack1) levels in parental NCI-H1975 and 67R cells. b The expression of p-Ack1 in NCI-H1975 xenograft tumors and 67R xenograft tumors was compared by immunoblotting. c The p-Ack1 protein in AZDR and NCI-H1975 was detected by immunoblotting. d Correlation analysis of Ack1 expression and relapse-free survival (RFS) of 204 lung adenocarcinoma cancer patients (GSE22138) is presented as a Kaplan-Meier plot. e The antiproliferation effects of ASK120067 on NCI-H1975 cells ectopically expressing negative control vector or Ack1 were assessed using an SRB assay. f Knockdown of Ack1 expression in 67R effectively enhanced the antiproliferation potency of ASK120067. g ASK120067 in combination with AIM-100 caused a significantly higher growth-inhibition rate in ASK120067-resistant cells than that with ASK120067 treatment alone. h AIM-100 synergistically enhanced the apoptosis-inducing activity of ASK120067 in 67R cells. Cells were treated with ASK120067, AIM-100 alone or both drugs in combination for 48 h, and apoptosis was assessed using flow cytometry. i and j Combination ASK120067 with dasatinib i or bosutinib j partially restored the growth-inhibition sensitivity of ASK120067-resistant cells to ASK120067 treatment. k Combination ASK120067 with AIM-100, dasatinib or bosutinib synergistically inhibited the growth of AZDR cells. Data are plotted as the mean ± SD, and significance of differences was evaluated by Student’s t test (∗p < 0.05, ∗∗p < 0.01)

Back to article page