The project aimed to identify changes at the protein level in human melanoma cells treated with the eIF4F inhibitor rocaglamide A, the MEK inhibitor PD184352 (CI-1040), and their combination. A375 and MelJuso human melanoma cell lines were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum, 1% penicillin/streptomycin, and 2 mM L-glutamine and maintained at 37 °C in a humidified atmosphere containing 5% CO2. For the analysis, both cell lines were seeded in 10-mm dishes and, the following day, treated with 100 nM rocaglamide A (DRG), 500 nM PD184352/CI-1040 (MEKi), and their combination (DRG_MEKi). Negative controls (CTR) were treated with an equivalent volume of DMSO. 20 h post-treatment, cells were washed with PBS, collected, and pelleted.