MEK inhibitors induce apoptosis via FoxO3a-dependent PUMA induction in colorectal cancer cells

a The indicated cell lines were treated with increasing doses of trametinib or selumetinib for 72？h. Cell proliferation was determined by MTS assay. b The indicated cell lines were treated with 0.1？μmol/L trametinib or 0.1？μmol/L selumetinib for 24？h at the indicated concentrations. Apoptosis was analyzed by Annexin V/PI staining followed by flow cytometry. c The indicated cell lines were treated with 0.1？μmol/L trametinib or 0.1？μmol/L selumetinib for 24？h at the indicated concentrations. Caspase 3/7 activity was determined by fluorogenic analysis. d The indicated cell lines were treated with 0.1？μmol/L trametinib or 0.1？μmol/L selumetinib at the indicated time points. Cleaved caspase 3, 8, and 9 were analyzed by Western blotting. The results in a, b, and c are expressed as the means？±？SD of three independent experiments. **P？<？0.01, *P？<？0.0