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 IC 50 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.