AKT1 and esophageal squamous cell carcinoma: Indeed, co-treatment with melatonin reverses the impact of 5-FU on the of activation MEK/Erk and GSK3β/Akt signaling pathway, which effectively leads to increased sensitivity to 5-FU in ESCC cells, as well as the cytotoxicity of 5-FU in ESCC [136].