Figure 2
From: Dual MET–EGFR combinatorial inhibition against T790M-EGFR-mediated erlotinib-resistant lung cancer
MET inhibition with SU11274 in EGFR-TKI-resistant H1975 lung cancer cells: induction of apoptosis in vitro and inhibition of cytoskeletal functions. The MET kinase inhibitor SU11274 was used to treat H1975 cells (L858R/T790M-EGFR, wild-type KRAS) and H520 cells (negative expression for both EGFR and MET) as control. The effect of SU11274 was examined using Annexin-V/propidium iodide (PI)-FITC cellular apoptosis assay. Untreated diluent control (U) and erlotinib were included in the experiment as treatment controls for comparison. Erlotinib (EGFR inhibition) was ineffective in promoting apoptosis in any of these above cell lines at 72 h. On the other hand, MET inhibition by SU11274 at 2 μ M induced significant cellular apoptosis in the EGFR-TKI-resistant H1975 cells (14.8±2.4%, P=0.0015), when compared with erlotinib (3.8±0.7%). For the EGFR-negative and MET-negative H520 cells, neither SU11274 (0.44±0.30%, P=0.22) nor erlotinib (0.28±0.13%, P=0.35) at 5 μ M induced any significant cellular apoptosis when compared with diluent control (0.18±0.10%). Mean values of percent cells in early apoptosis (Annexin-V plus PI staining) from three independent experiments for each of the treatment conditions were plotted in the graphs shown here. Error bar, s.e.m. (N=3).
