Benzo[a]pyrene at human blood equivalent level induces human lung epithelial cell invasion and migration via aryl hydrocarbon receptor signaling

Abstract Benzo[ a ]pyrene (B[ a ]P), a typical carcinogenic polycyclic aromatic hydrocarbon, exists worldwide in vehicle exhaust, cigarette smoke and other polluted environments. Recent studies have demonstrated a strong association between B[ a ]P and lung cancer. However, whether B[ a ]P at human blood equivalent level can promote epithelial‐mesenchymal transition (EMT), a crucial molecular event during cell malignant transformation, remains unclear. Besides, whether B[ a ]P facilitates this progress via aryl hydrocarbon receptor (AhR) signaling pathway also lacks scientific evidence. In our study, the transwell assay showed that 5 μg/L of B[ a ]P promoted BEAS‐2B cell invasion and migration. In addition, the mRNA and protein expression levels of AhR and its target genes involved in B[ a ]P metabolism, such as AhR nuclear translocator, heat shock protein 90 and CYP1A1, were significantly increased by B[ a ]P exposure. Moreover, the mRNA expression levels of downstream regulatory factors related to both AhR signaling pathway and EMT, such as NRF2, K‐RAS and hypoxia‐inducible factor 1‐alpha, were significantly increased. Furthermore, the expression level of the epithelial marker E‐cadherin was significantly downregulated, while the mRNA expression of mesenchymal phenotype markers, N‐cadherin, fibronectin and vimentin, were significantly upregulated. Notably, the above changes induced by B[ a ]P were significantly attenuated or even stopped by resveratrol (RSV), a natural phenol, also an AhR inhibitor, when the AhR signaling pathway was inhibited by RSV, demonstrating the regulatory role of AhR signaling pathway in B[ a ]P‐induced EMT. In conclusion, B[ a ]P at the human blood equivalent level induces BEAS‐2B cell invasion and migration through the AhR signaling pathway.