6PPD-quinone promotes ovarian cancer progression: Insights from network toxicology, machine learning, and in vitro validation.

6PPD-quinone (6PPD-Q), a toxic tire-derived antioxidant transformation product, is a pervasive environmental contaminant linked to reproductive toxicity. However, its role in ovarian cancer (OC) remains elusive. We integrated network toxicology with transcriptomic analysis to elucidate the oncogenic mechanisms of 6PPD-Q. By screening the GEO, SwissTargetPrediction, and SEA databases, we identified 26 intersection targets. Utilizing machine learning and SHAP analysis, five core biomarkers-DDR1, ABL1, PDE2A, FRK, and F10-were prioritized. Molecular docking demonstrated high binding affinities between 6PPD-Q and these core proteins. In vitro validation, including CCK-8, plate colony formation, and qRT-PCR assays, confirmed that 6PPD-Q exposure significantly promotes OC cell proliferation. Mechanistically, 6PPD-Q may regulate the expression of hub targets to affect OC progression. This study establishes a definitive "exposure-target-phenotype" chain, characterizing 6PPD-Q as a potential environmental promoter of OC and suggest potential intervention targets.