TY - JOUR ID - 232189 TI - The Influence of 5-Fluorouracil on Drug Transporters is a Dose-Dependent Effect Mediated by Altered Expression of miRNAs JO - Egyptian Journal of Chemistry JA - EJCHEM LA - en SN - 0449-2285 AU - Eldaly, Sherien M. AU - Gouhar, Shaimaa A. AU - Abo-elfadl, Mahmoud T. AD - Medical Biochemistry Department- Medicine and Clinical Studies Research Institute - National Research Centre - Cairo - Egypt AD - Cancer Biology and Genetics Laboratory Centre of Excellence for Advanced Sciences, National Research Centre Y1 - 2022 PY - 2022 VL - 65 IS - 8 SP - 737 EP - 748 KW - 5-Fluouracil - Colorectal cancer - ABCC2 - ABCG2 - miR-27a KW - miR-31- miR-200c DO - 10.21608/ejchem.2022.132340.5844 N2 - 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. UR - https://ejchem.journals.ekb.eg/article_232189.html L1 - https://ejchem.journals.ekb.eg/article_232189_825b8e16d4015794c79633029e40cd56.pdf ER -