Dose‑reducing synergistic effects of doxorubicin and 5‑fluorouracil on triple‑negative breast cancer cells
Year: 2026
Type: article
Abstract: Triple-negative breast cancer (TNBC) is an aggressive subtype of cancer with limited treatment options.Despite the use of both doxorubicin (Doxo) and 5-fluorouracil (5-FU) as part of the FAC regimen, their interaction in TNBC has not yet been studied in detail, at least to the best of our knowledge.As reducing toxicity while preserving therapeutic efficacy remains a key therapeutic goal, the present in vitro study investigated whether the combination of Doxo and 5-FU exerts synergistic effects on MDA-MB231 cells and enables dose reduction.MTT assays were used to measure the viability of the TNBC cell line, MDA-MB-231 and non-transformed rat embryo fibroblasts (REFs) following exposure to Doxo and 5-FU, alone or in combination, for 72 h.Synergistic effects were evaluated using the combination index (CI) calculated using CalcuSyn software.Cell morphology was assessed by inverted microscopy, and apoptosis was assessed using acridine orange/ethidium bromide dual staining followed by fluorescence microscopy.The dose-response data revealed anti-proliferative effects in MDA-MB-231 cells (GI 50 =8.57and 34.38 µM for Doxo and 5-FU, respectively) and REF cells (GI 50 =1.3and 48.66 µM, respectively).Combination treatment reduced the concentrations of Doxo and 5-FU required to achieve the GI 50 by 27.9 and 85.5%, respectively, compared with monotherapy.This dose-sparing effect was accompanied by a modest increase in apoptosis and marked morphological alterations.To the best of our knowledge, the present study is the first to quantitatively characterize the synergistic interaction between Doxo and 5-FU in TNBC cells, providing evidence of clinically relevant dose reduction beyond the historical empirical use of the FAC regimen.
Authors: Ali Alhammer, Fadhel Lafta, Shahad Mudhafar
Institutions: Nahrain University, University of Baghdad
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7203897756