Lycorine enhances the anti-cancer effects of vemurafenib. (A) HCT116 cells transfected with blank shRNA or shMEK2 were treated with or without lycorine, and western blotting was performed to investigate the changes in autophagy and apoptosis. GAPDH was used as a loading control. (B) Mitogen-activated protein kinase kinase 2 (MEK2) was depleted in MEK2-overexpressing HCT116 cells by exposure to lycorine, and western blotting was used to investigate the levels of autophagy and apoptosis. GAPDH was used as a loading control. (C–D) The viability of HCT116 cells transfected with control or MEK2 vectors in response to different treatments (lycorine, vemurafenib, lycorine plus vemurafenib) was detected using the Cell Counting Kit-8 assay. (E–F) SW480, HCT116, and MEK2-overexpressing cells were treated with lycorine, vemurafenib, or lycorine + vemurafenib for 24 h and analyzed using annexin V/PI flow cytometry. The right lower quadrant indicates early apoptosis. Data are presented as the mean ± SD of three independent experiments (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).