In addition, a melittin analog (MEL-pep) directly inhibited P-gp expression and increased the intracellular accumulation of rhodamine-123, a P-gp substrate, in 5-fluorouracil-resistant HCC cells, an effect linked to the deactivation of the PI3K/Akt pathway [106]. This evidence concerns the gene AKT1 and hepatocellular carcinoma.