Therapeutic effects of selenium-enriched rapeseed against triple-negative breast cancer: involvement of Resolvin D5 activation and IL-17 signaling inhibition.

Triple-negative breast cancer (TNBC) presents a major therapeutic challenge due to its aggressive behavior and a microenvironment characterized by a dysregulated axis linking inflammation to tumor progression. As a selenium-biofortified edible vegetable, selenium-enriched rapeseed shoots (SeRS) are a promising dietary source of methylselenocysteine (MSC), highlighting their potential in "medicine-food homology" strategies. This study aimed to investigate the chemo-preventive efficacy of selenium-enriched SeRS as a dietary intervention in TNBC, building upon its previously documented anti-inflammatory and antioxidant properties, and to elucidate its underlying mechanism of action. We first demonstrated that SeRS aqueous extract significantly inhibited the migration and invasion of 4T1 TNBC cells . Subsequently, in a preventive dietary intervention study, administration of SeRS potently suppressed orthotopic tumor growth and metastasis in a 4T1 syngeneic mouse model. Concomitantly, SeRS treatment favorably remodeled the tumor immune microenvironment, as evidenced by increased infiltration of CD4 and CD8 T cells and a decrease in exhausted PD-1/LAG-3 T cell subsets. Integrated metabolomic and transcriptomic analyses identified resolvin D5 (RvD5), a specialized pro-resolving mediator, as a key endogenous metabolite upregulated by SeRS, and revealed the pro-inflammatory IL-17 signaling pathway as a potential target. Molecular docking confirmed high-affinity binding between RvD5 and IL-17A. Functionally, both SeRS and purified RvD5 suppressed IL-17 pathway activation, as evidenced by reduced phospho-p65 and downregulation of IL-17 receptor (IL-17RA) and ACT-1. Critically, rescue experiments established that RvD5 could reverse IL-17A-induced pro-tumorigenic effects. Our findings elucidate a coordinated mechanism in which SeRS, upregulation of RvD5, suppresses the IL-17 signaling pathway-a key driver of chronic inflammation and immune dysfunction in TNBC-thereby exerting anti-TNBC effects. This work provides a scientific basis for developing selenium-enriched agricultural products into functional foods for cancer prevention through targeted nutritional modulation.