Fig. 4

Targeting Src overcomes IGF-1R TKI resistance in vitro both in high-pSrc-expressing and low-pSrc-expressing NSCLC cells. The effects of linsitinib, either alone or in combination with dasatinib, on viability (a and f), anchorage-dependent (b and g), and anchorage-independent (h) colony formation, and apoptosis (d, e and i) were determined. The induction of apoptosis was analyzed by flow cytometry after staining with annexin V-FITC and PI (d) and Western blot analysis on PARP and caspase-3 cleavages (e and i). The bars represent the means ± SD; *P < 0.05, **P < 0.01, and ***P < 0.001. (c) Cells were transfected with scrambled or Src siRNAs. Transfected cells were seeded into 6-well plates at a density of 150 cells/well to evaluate the inhibitory effect of linsitinib on the anchorage-dependent growth as described in Supplemental Information. The bars represent the means ± SD; *P < 0.05 and ***P < 0.001