Figure 5

DDR pathway contributes to osimertinib resistance in selumetinib-treated NSCLC cells. (a) OR cell toxicity assay in response to increasing concentrations of DDRi (PARP-I, ATM-I, DNA-PK-I, AURK-A-I, ATR-I, benzosertib) in combination with selumetinib (2.5 μM) for 72 h. (b) Levels of DDR markers (p-DNA-PK, DNA-PK, p-H2A.X, H2A.X, AURK-A) in response to treatment with selumetinib (2.5 µM) for 72 h. GAPDH was used to ensure equal loading. (c) Immunoprecipitation assay with anti-p53 antibody in whole cell lysates and (d) representative western bot images of DNA-PK, AURK-A and p53 in input samples from PC9, PC9/OR, H1975 and H1975/OR treated or not with selumetinib (2.5 μM) alone or in combination with AURK-A-I (2 μM) or DNA-PK-I (2 μM), respectively. Tubulin was used to ensure equal loading.