Fig. 2: Adaptive resistance cells active oxidative phosphorylation (OXPHOS).

a Metabolomics analysis of H1975 cells treated with Osi for 0 h (Parental), 24 h, and 72 h (Adapted) (n = 3 samples). b KEGG pathway enrichment analysis was performed on the metabolite comparing adapted cells versus parental cells. c, d Volcano plot displaying different metabolites after 24 h or 72 h Osi treatment in H1975 cells. e H1975 and HCC827 cells were harvested after 0 h (Parental) or 72 h (Adapted) Osi treatment and analyzed by electron microscopy for mitochondrial morphology (n = 4 technical replicates; 3 independent experiments). Scale bar, 1 μm. f Specific mean fluorescence intensity (MFI) of MitoTracker in Parental and Adapted cells. Representative experiment (n = 4 technical replicates; 3 independent experiments). g The ratio of mitochondrial DNA to nuclear DNA in Parental and Adapted cells. Representative experiment (n = 9 technical replicates; 3 independent experiments). h Relative citrate synthase (CS) activity in Parental and Adapted cells. Representative experiment (n = 9 technical replicates; 3 independent experiments). i Representative immunoblotting of ETC proteins in H1975 and HCC827 cells treated with DMSO or Osi for 0 h, 24 h, and 72 h (Representative images from 3 independent experiments). j–l The representative pattern of OCR over time j, basal OCR values k and maximal OCR values l normalized to total protein levels. Representative experiment (n = 3 technical replicates; 3 independent experiments). m Basal EACR in control conditions or the presence of 10 mM glucose (Glc) in Parental and Adapted cells. Representative experiment (n = 3 technical replicates; 3 independent experiments). n Cell Energy Phenotype analyses of the Parental and Adapted cells through real-time quantifications of ECAR and OCR at baseline or stressed with Oligo-A/FCCP. Representative experiment (n = 3 technical replicates; 3 independent experiments). o, p Colony formation assays of Parental and Adapted H1975 or HCC827 cells at 0 h, treated with DMSO for 12 h, and treated with an increasing concentration of oligo-A or rotenone for 12 h. Representative experiment (n = 3 technical replicates; 3 independent experiments). Data are shown as mean ± SD and were analyzed by a two-tailed unpaired t-test e–l or a two-way ANOVA m, o, p. NS no significance, ***p < 0.001. ^†††p < 0.001, which was employed to specifically demonstrate the distinction in HCC827 cells. For box plots, the boxes extend from the 25th to 75th percentiles, with the median depicted by a horizontal line. Source data are provided as a Source Data file.