Curcumin Reverses 5-Fluorouracil Resistance in HCT8/5-FU Colon Cancer Cells via the Ferroptosis Pathway: An In Vitro Study

Background: Colorectal cancer (CRC) resistance to 5-fluorouracil (5-FU) remains a major challenge. Recent studies suggest that curcumin may enhance 5-FU's effectiveness by modulating ferroptosis. This study sought to determine whether curcumin may reverse 5-FU resistance in HCT8/5-FU colon cancer cells in vitro. Materials and Methods: Research models were HCT8 and HCT8/5-FU colon cancer cells. The CCK-8 assay was used to measure the drug resistance index of HCT8/5-FU cells and the impact of varying doses of curcumin combined with 5-FU on cell growth. Malondialdehyde (MDA) levels were assessed using an MDA testing kit, and reactive oxygen species (ROS) levels were evaluated using flow cytometry. Cell migration and invasion capabilities were examined using Transwell and wound-healing assays. Ferroptosis-related protein expression was measured by Western blotting, and the mRNA expression levels of these proteins were evaluated by qRTPCR. Results: With a reversal fold of 2.34, curcumin significantly overcame 5-FU resistance in HCT8/5-FU cells. The combination of 5-FU and curcumin suppressed the expression of the enzymes Solute Carrier Family 7 Member 11 (SLC7A11) and Glutathione Peroxidase 4 (GPX4), increased intracellular ROS and MDA levels, and inhibited cell migration and invasion. These effects were counteracted by the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Discussion: Curcumin promotes ferroptosis to enhance 5-FU sensitivity, indicating its potential to counter colorectal cancer chemoresistance. Conclusions: Curcumin modulates the ferroptosis pathway in vitro to restore 5-FU sensitivity in HCT8/5-FU colon cancer cells, suggesting its potential use as a therapeutic agent to overcome chemoresistance in colorectal cancer.