Melatonin enhances the sensitivity of colorectal cancer cells to 5-fluorouracil through the regulation of the miR-532-3p/β-catenin pathway.

Abstract

This research aimed to investigate whether melatonin affected sensitivity to 5-fluorouracil (5-FU) in colorectal cancer (CRC) as well as to show the underlying molecular mechanism. Melatonin and 5-FU were added to CRC cells at varying doses. The effect of melatonin on sensitivity to 5-FU was investigated by measuring cell activity and apoptosis, and the potential underlying mechanism was further explored by detecting miR-532-3p expression and the associated pathway proteins. Melatonin could suppress cell malignancy in SW480 and HCT116 cells. Melatonin also significantly promoted sensitivity to 5-FU in CRC cells. miR-532-3p expression was downregulated in CRC and was also markedly enhanced when treated with 1 mmol/L melatonin. The inhibitory ability of the co-cultured melatonin, 5-FU, and miR-532-3p inhibitor on SW480 and HCT116 cells was markedly diminished, and the IC50 value was significantly enhanced. Relative to the melatonin group, melatonin+miR-532-3p inhibitor markedly declined apoptosis rate. Bioinformatics analysis predicted the target of miR-532-3p. β-catenin level presented obvious downregulation in the melatonin group, while it was notably upregulated in the co-culture group in relative to with that in the melatonin group. Overall, melatonin promotes sensitivity to 5-FU in CRC cells by regulating the miR-532-3p/β-catenin pathway.