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

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/β-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/β-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/β-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/β-catenin signalling pathway in CRC, which advocates further research of this combination with the lower dose of 5-FU.