Multi omics network toxicology and in vitro experiments elucidate the role of benzo [a] pyrene in prostate cancer

Background In recent years, growing attention has been paid to the role of Benzo [a]pyrene (BaP) in the development and progression of prostate cancer (PCa). However, the specific molecular mechanisms remain unclear. This study aims to explore the potential association between BaP and PCa and to identify key molecular targets that may underlie this relationship, using an integrative bioinformatics approach. Methods This study initiated with a computational toxicology assessment of BaP’s carcinogenicity and endocrine-disrupting properties using the ProTox 3.0 platform. Subsequently, potential target genes linking BaP to PCa were identified by integrating multiple public databases. The overlapping genes underwent PPI network construction and visualization, followed by GO functional annotation and KEGG pathway enrichment analyses to elucidate the underlying biological mechanisms. Through screening 101 machine learning algorithm combinations, we identified the most relevant key genes associated with PCa progression. Molecular docking technology was then employed to evaluate the binding interactions between BaP/natural active products and these key targets. The CIBERSORT algorithm was utilized to analyze RRM2’s regulatory role in the PCa tumor microenvironment, complemented by pan-cancer analysis to investigate RRM2’s universal functions across various malignancies. Finally, in vitro cell experiments were conducted for validation. Results This study further underscores the carcinogenic properties and endocrine-disrupting effects of BaP. Integration of multi-source databases identified 443 potential BaP-PCa targets. GO and KEGG enrichment analyses revealed that these targets are primarily involved in regulating cell proliferation, inflammatory responses, oxidative stress, and multiple oncogenic signaling pathways. Machine learning algorithm screening showed that the Enet (α = 0.1) model exhibited the best predictive performance and robustness. Through molecular docking, Kaplan-Meier survival analysis, and validation using the Human Protein Atlas (HPA) database, RRM2 was identified as a key regulatory gene and found to play a central role in BaP-mediated immunosuppression processes. Pan-cancer analysis demonstrated that RRM2 has universal functions across various malignancies. Molecular docking results indicated that seven known anti-tumor natural products exhibit significant binding affinity with RRM2. In vitro experiments demonstrated that BaP treatment was associated with increased RRM2 expression in prostate cancer cells, while baicalin treatment reduced this effect, providing preliminary experimental support for the bioinformatic predictions. Conclusion This study delineates a potential mechanistic framework by which BaP may be associated with PCa progression through multi-target and multi-pathway mechanisms, highlighting RRM2 as a candidate core mediator. These findings provide a theoretical foundation for future experimental validation and epidemiological studies.