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Published on: November 2, 2014
6PPD-quinone promotes ovarian cancer progression: Insights from network toxicology, machine learning, and in vitro
Nannan Wang1, Jingyu Zhu1, Ningjuan Wu1
1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, PR China.
Abstract:
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.
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