Fig. 1: Osi treatment rapidly induces adaptative resistance in tumor cells.

a BALB/c nude mouse lungs were orthotopically transplanted with Luc-H1975 or Luc-HCC827 cells and were given Vehicle or Osi and follow-up using bioluminescence imaging (BLI) (n = 5 mice each group). b, c Quantification of the relative fluorescence activity of the region of interest (ROI) in mice by BLI reflects the growth of mice lung tumors (n = 5 mice each group). d Doubling time of lung tumors reflects the fold-change (FC) to pre-treatment based on the relative strength of the ROI region in mice by BLI (n = 5 mice each group). e Left, Hematoxylin-eosin (H&E, 1×) and immunohistochemistry (IHC, 40×) analysis of mouse lungs from a to c on day 40 (H1975 tumors) and day 50 (HCC827 tumors). Scale bar, 1×, 2 mm; 40×, 50 μm. Right, statistics of lung tumor size and percent Ki-67 positive cells were obtained after Vehicle or Osi treatment, respectively (n = 5 tumors each group). f–h BALB/c nude mouse subcutaneously inoculated with H1975 or HCC827 cells were given Vehicle or Osi treatment. A subset of mice from each group were sacrificed, and their subcutaneous tumors were excised for IHC analysis (n = 9 mice each group). i H1975 and HCC827 cells treated with Osi in 3-D culture on day 1, day 3, and day 8. Representative experiment (n = 3 technical replicates; 3 independent experiments). Scale bar, 10 μm. j H1975 and HCC827 cells were treated with Osi for 0 h, 24 h, or 72 h and incubated with 5-ethynyl-2’-deoxyuridine (EdU) for 2 h. Representative experiment (n = 3 technical replicates; 3 independent experiments). Scale bar, 100 μm. k Flow cytometry analysis of cell cycles of H1975 and HCC827 cells treated with DMSO or Osi for 0 h, 24 h, or 72 h. Representative experiment (n = 3 technical replicates; 3 independent experiments). l Flow cytometry analysis of cell apoptosis in H1975 and HCC827 cells treated with DMSO or Osi for 0 h, 24 h, or 72 h. Representative experiment (n = 3 technical replicates; 3 independent experiments). m Immunoblotting analysis of apoptosis-related proteins PARP and Capase-3 (Cas-3) in H1975 and HCC827 cells treated with DMSO or Osi for 0 h, 24 h or 72 h (Representative images from 3 independent experiments). Data are shown as mean ± SD and were analyzed by a two-tailed unpaired t-test (d,e) or a two-way ANOVA g–l. NS no significance, *p < 0.05, **p < 0.01, ***p < 0.001. ^†p < 0.05, ^††p < 0.01, ^†††p < 0.001, which was employed to specifically demonstrate the distinction in HCC827 cells. Source data are provided as a Source Data file.