Low-dose polysaccharides exert dual redox effects via the ROS-mediated MAPK pathway: Antioxidant alone or pro-oxidant when GLP is combined with doxorubicin in A2780 ovarian cancer cells.

Ovarian cancer (OC) is a lethal gynecological malignancy. Patients usually consume low doses of natural polysaccharides through their diet as exogenous antioxidants. This study aims to explore the dual effects of low doses of five natural polysaccharides (GLP, LBP, LNT, APS, FUC) on A2780 OC cells, as well as the underlying molecular mechanisms. The redox effects of their individual actions and the combined action of GLP and doxorubicin (DOX) were evaluated by ROS, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) assays; their growth/apoptosis effects were assessed by MTT, colony formation and flow cytometry. Network pharmacology predicted the MAPK pathway, which was verified by Western blot. In vivo, a xenograft model was established to evaluate the effect of the combination of GLP and DOX. The results showed that low doses of polysaccharides reduced ROS levels, promoted cell viability and colony-forming capacity, upregulated p-ERK levels, and downregulated p-p38 and p-JNK. In vitro, the same dose of GLP combined with DOX increased ROS levels, inhibited cell growth, induced apoptosis, and activated all three MAPK subfamilies. The ROS scavenger N-acetylcysteine (NAC) reversed these effects. In vivo, GLP combined with DOX synergistically inhibited tumor growth. Low doses of natural polysaccharides have specific dual effects: when used alone, they have antioxidant effects, but when GLP is combined with DOX, they have pro-oxidant and tumor-suppressive effects. Both of these effects are mediated through the ROS-MAPK pathway. This provides an experimental basis for mechanism studies and clinical applications of chemotherapy combined with polysaccharides in epithelial OC.