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.

中文翻译：

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褪黑素通过调节miR-532-3p/β-catenin通路增强结直肠癌细胞对5-氟尿嘧啶的敏感性


本研究旨在探讨褪黑激素是否影响结直肠癌 (CRC) 对 5-氟尿嘧啶 (5-FU) 的敏感性，并揭示其潜在的分子机制。将不同剂量的褪黑激素和 5-FU 添加到 CRC 细胞中。通过测量细胞活性和凋亡来研究褪黑素对 5-FU 敏感性的影响，并通过检测 miR-532-3p 表达和相关通路蛋白进一步探讨潜在的潜在机制。褪黑素可以抑制 SW480 和 HCT116 细胞的细胞恶性肿瘤。褪黑激素还显着提高 CRC 细胞对 5-FU 的敏感性。 miR-532-3p 表达在结直肠癌中下调，并且在用 1 mmol/L 褪黑激素处理后也显着增强。共培养的褪黑素、5-FU和miR-532-3p抑制剂对SW480和HCT116细胞的抑制能力明显减弱，IC ₅₀值明显增强。相对于褪黑素组，褪黑素+miR-532-3p抑制剂显着降低了细胞凋亡率。生物信息学分析预测了miR-532-3p的靶点。褪黑素组β-catenin水平明显下调，而共培养组较褪黑素组β-catenin水平明显上调。总体而言，褪黑激素通过调节 miR-532-3p/β-catenin 通路提高 CRC 细胞对 5-FU 的敏感性。