Quercetin potentiates 5-fluorouracil effects in human colon cancer cells through targeting the Wnt/ß-catenin signalling pathway: the role of miR-27a.

ABSTRACT

Introduction: 5-fluorouracil (5-FU) is the most widely used chemotherapeutic drug in treating colorectal cancer. However, its toxicity to normal tissues and tumour resistance are the main hurdles to efficient cancer treatment. MiR27-a promotes the proliferation of colon cancer cells by stimulating the Wnt/ß-catenin pathway. The present study was conducted to examine whether quercetin (Q) combined with 5-FU improves the anti-proliferative effect of 5-FU on HCT-116 and Caco-2 cell lines through detection of the miR-27a/Wnt/ß-catenin signalling pathway. Material and methods: Cell viability in HCT-116 and Caco-2 cell lines following quercetin and 5-FU treatment alone and in combination for 48 hours was determined using the MTT assay. The flow cytometry, quantitative real-time polymerase chain reaction, and ELISA techniques were used. Results: Our results showed that combination of quercetin and 5-FU exhibited greater cytotoxic efficacy than did 5-FU alone. Co-administration of both drugs either in combination 1 (1 1 Q 5-FU) or in combination 2 (1 0.5 Q 5-FU) enhanced apoptosis in HCT-116 and Caco-2 cells compared with 5-FU alone and significantly inhibited the expression of miR-27a, leading to upregulation of secreted frizzled-related protein 1 and suppression of Wnt/ß-catenin signalling, which was confirmed by a significant decrease in cyclin D1 expression. Conclusions: Quercetin strongly enhanced 5-FU sensitivity via suppression of the miR-27a/Wnt/ß-catenin signalling pathway in CRC, which advocates further research of this combination with the lower dose of 5-FU.