Targeting the OXNAD1-PTGS2 axis with resveratrol overcomes ferroptosis Inhibition and reverses 5-FU resistance in gastric cancer - PubMed
5 hours ago
- #5-FU resistance
- #Ferroptosis
- #Gastric cancer
- 5-Fluorouracil (5-FU) is a first-line chemotherapy for gastric cancer, but resistance reduces its efficacy.
- Ferroptosis suppression is a key mechanism of chemoresistance, with mitochondrial processes not well understood.
- OXNAD1, a mitochondrial oxidoreductase, is overexpressed in gastric cancer and linked to poor prognosis and 5-FU resistance.
- OXNAD1 binds to and inhibits PTGS2, a ferroptosis driver, reducing lipid peroxidation and mitochondrial damage, thus promoting resistance.
- Resveratrol disrupts the OXNAD1-PTGS2 interaction by binding OXNAD1, restoring ferroptosis and enhancing 5-FU's cytotoxic effect in resistant cells.
- In vivo studies show resveratrol boosts 5-FU's antitumor efficacy in xenograft models.
- Targeting the OXNAD1-PTGS2 axis with resveratrol offers a promising strategy to overcome 5-FU resistance in gastric cancer.