Figure 2
Dabrafenib inhibits RIP3-mediated necroptosis. (a) Cell viability was examined in HT29 cells with or without TNFα (20 ng/ml) plus Smac mimetic (100 nM) and the caspase inhibitor z-VAD (20 μM; TSZ) in the presence of the indicated compounds (dabrafenib, 10 μM; all the others, 100 μM) for 24 h. (b) HT29 cells exposed to TSZ for 24 h in the presence or absence of 10 μM dabrafenib were observed under an inverted microscope at 20 × magnification. Scale bar, 50 μm. The data were representative of three independent experiments. (c) The cell viability of N and A cells (upper panel) or the RIP3-silenced N cells (lower panel) exposed to TSZ or TSZ plus dabrafenib for 24 h was determined. The protein levels of RIP3 in the cells were examined by western blotting. *P=0.002; **P=0.001. shNC and shRIP3, N cells transfected with the control shRNA and RIP3 shRNA, respectively. (d) The effects of the indicated compounds on cell viability were examined in HT29 cells or U937 cells treated with TSZ for 24 h. (e) The cell viability of HT29 cells treated with SZ plus 1 μg/ml Fas ligand or 200 ng/ml TRAIL was examined in the presence or absence of 10 μM dabrafenib. *P=0.003; **P=0.0003
