3.8 Article

The Influence of 5-Fluorouracil on Drug Transporters is a Dose-Dependent Effect Mediated by Altered Expression of miRNAs

Journal

EGYPTIAN JOURNAL OF CHEMISTRY
Volume 65, Issue 8, Pages 737-748

Publisher

NATL INFORM & DOCUMENT CENTRE
DOI: 10.21608/EJCHEM.2022.132340.5844

Keywords

5-Fluouracil; colorectal cancer; ABCC2; ABCG2; CYP3A4; miR-27a; miR-31; miR-200c

Funding

  1. Science and Technology Development Fund (STDF) - Research Support Grant [26388]

Ask authors/readers for more resources

This study aimed to investigate the dose-dependent effect of 5-fluorouracil (5-FU) on the expression of drug transporters and miRNAs in colorectal cancer. The results showed that a low dose of 5-FU upregulated the expression of drug transporters and miRNAs, while increasing the dose led to a decrease in expression.
ATP-binding cassette (ABC) transporters are crucial in transporting nutrients into cells and expelling xenobiotics out of cells to ensure cell viability. Several investigations have shown interactions between drug transporters and anti-cancer drugs. Overexpression of drug transporters is a primary factor leading to multi-drug resistance (MDR), which may facilitate the efflux of many chemotherapeutics from cancer cells, hence reducing intracellular drug concentration. In the present study, we aimed to delineate the dose-dependent effect of one of the most applied chemotherapeutic drugs, 5-fluorouracil (5-FU), on the expression of drug transporters in colorectal cancer. We investigated the effect of different doses of 5-FU on the expression of a panel of ABC transporters, and we also evaluated the differential expression of miRNAs involved in drug resistance. Our study revealed that a low dose of 5-FU can upregulate ABCC2, ABCG2, ABCB1, and ABCC5 transporters significantly. However, by increasing the dose of 5-FU, the expression of these drug transporters decreased dynamically. The same pattern of expression was also detected in miRNAs, where the lowest dose of 5-Fu was responsible for the highest elevation in miR-27a, miR-31, and miR-200c levels, and by increasing the dose of 5-FU, this elevation significantly decreased. Our results suggest that a low dose of 5-FU may promote the development of drug resistance in colorectal cancer by enhancing drug transporters, stressing the need of adopting a chemotherapeutic dose that has an acceptable cytotoxic impact while also being effective in reducing the activity of drug transporters

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

3.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available