Cell adaptation to ERK1/2 and MEK1/2 inhibitors.A, ERK1/2 activity and (B) cell proliferation in H1299, HCT-116, and SH-SY5Y cells treated with MEK1/2 and ERK1/2 inhibitors for 12 days. For H1299 and SH-SY5Y 100 nM drug concentration was used, and 50 nM was used for HCT-116 cells. Medium change and addition of fresh inhibitors in the same concentrations was performed after 4 and 8 days of treatment. C, cell viability measurement for cells treated with dimethyl sulfoxide (DMSO-treated) or PD0325901 (PD-treated) for 12 days and then treated with PD0325901, ulixertinib, and SCH772984 for 96 h.