A. H1299 cells were treated with melatonin (MT, 1.0 mM) and berberine (BBR, 20 or 100 μM). At 48 hours after treatment, the expression of the total and phosphorylated Akt and ERK1/2 proteins were determined by Western blot. B, C. H1299 cells were treated with the Akt-selective inhibitor LY294002 (LY, 30 μM) (B) or the Mek1/2-selective inhibitor U0126 (50 μM) (C) for 24 hours, respectively, and then treated with melatonin (MT, 1.0 mM) and berberine (BBR, 100 μM). At 48 hours after treatment, cell viability was determined by MTT analysis. The percent cell viability in each treatment group was calculated relative to cells treated with the vehicle control. The data are presented as the mean ± SD of three separate experiments. *P < 0.05, significant differences between treatment groups and control groups.