SOD2 promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer

Helicobacter pylori (H. pylori) infection is the most common risk factor for gastric cancer (GC). The effect of the antioxidase manganese superoxide dismutase (SOD2) in gastric tumorigenesis remains unclear. We explored the molecular and mechanical links between H. pylori, inflammation, and SOD2 in GC. We found SOD2 was upregulated in GC. GC patients with high SOD2 expression showed worse overall survival. H. pylori infection promoted SOD2 expression by transcriptionally activating the NF-?B signaling pathway. Knockdown of SOD2 led to increased levels of reactive oxygen species and oxidative stress in response to H. pylori infection. Our research demonstrated that SOD2 can serve as an inhibitor of ferroptosis by activating AKT, stabilizing GPX4 protein, which subsequently induces 5-fluorouracil resistance. These findings reveal a mechanism whereby H. pylori can promote gastric carcinogenesis by activating the NF-?B/SOD2/AKT/GPX4 pathway, leading to the inhibition of ferroptosis. This may provide a promising therapeutic target for GC. Overall design: MGC803 gastric cancer cells co-cultured with or without H. pylori for 6 h (n=3)