Melatonin sensitizes esophageal cancer cells to 5-fluorouracil via promotion of apoptosis by regulating EZH2 expression

The present study aimed to investigate the effects of melatonin (MLT) and 5-fluorouracil (5-FU) combination on the chemotherapeutic effect of 5-FU in esophageal cancer, and determine the potential molecular mechanisms. The effects of MLT and 5-FU combination on cell proliferation, cell migration and invasion, and cell apoptosis were detected by Cell Counting Kit-8, Transwell assays and flow cytometric analysis, respectively. Quantitative PCR and western blotting were performed for mRNA and protein quantification, respectively. The present study revealed that MLT significantly inhibited cell activity in a dose-dependent manner and MLT significantly enhanced 5-FU-mediated inhibition of cell proliferation in esophageal cancer cells. Compared with the 5-FU group, the MLT and 5-FU combination group significantly inhibited the invasion and migration of EC-9706 and EC-109 cells. The present study also revealed that MLT and 5-FU synergistically promoted apoptosis via activation of the caspase-dependent apoptosis pathway. Histone-lysine N-methyltransferase EZH2 (EZH2) was highly expressed in esophageal cancer tissues and cells and its high expression promoted esophageal cancer progression. MLT and 5-FU combination inhibited cell proliferation and promoted apoptosis by regulating EZH2 expression. In conclusion, MLT enhanced 5-FU-mediated inhibition of cell proliferation via promotion of apoptosis by regulating EZH2 expression in esophageal cancer.