eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
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SCImago Journal & Country Rank
3/2022
vol. 26
 
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abstract:
Original paper

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

Ghada T. Terana
1
,
Mohamed M. Abd-Alhaseeb
2
,
Gamal A. Omran
1
,
Tarek M. Okda
1

1.
Department of Biochemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
2.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
Contemp Oncol (Pozn) 2022; 26 (2): 229–238
Online publish date: 2022/10/24
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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.

keywords:

colorectal cancer, 5-fluorouracil, quercetin, miR-27a, Wnt/β- catenin

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