Aspirin inhibited the Warburg effect induced by Ni-refining fumes via the Wnt/β-catenin pathway in Beas-2B cells

Abstract The natural metal nickel (Ni) can be found in the air, water, sediment, and soil. Although epidemiological research and experimental data have shown that nickel is linked to lung cancer, the precise mechanism of nickel carcinogenesis is unclear. We investigated whether Ni-refining fumes stimulated the Wnt/β-catenin pathway and caused the Warburg effect in Beas-2B cells, then if aspirin could protect the cells. The findings demonstrated that Beas-2B cells were significantly toxicated by Ni-refining fumes. With the increase of Ni-refining fumes concentration, the proteins and mRNAs level of the Wnt/β-catenin pathway were significantly increased and Warburg effect-related proteins: pyruvate dehydrogenase kinase 1 (PDK1), monocarborxylat transporter 1 (MCT1) and lactate dehydrogenase A (LDHA) also increased significantly. Pyruvate dehydrogenase (PDH) activity was reduced and reactive oxygen species (ROS) production was increased. When given the Wnt/β-catenin pathway inhibitor XAV-939, Warburg effect-related proteins expression can be inhibited. Aspirin at various concentrations could improve the relative viability of cells exposed to nickel refining fumes, with 2.5 mmol/L aspirin providing the most significant protection (P<0.05). Compared with the nickel staining group, aspirin treatment significantly decreased the expression of the Wnt/β-catenin pathway and Warburg effect-related proteins whereas it inhibited the production of ROS, too.