Low Dose of Bisphenol A Activates NF-κB/IL-6 Signals to Increase Malignancy of Neuroblastoma Cells

Bisphenol A (BPA) can accumulate in the human body and promote the progression of various cancers. However, its role in the development of neuroblastoma (NB) is largely unknown. Our present study revealed that nanomolar concentrations of BPA can significantly increase the proliferation, migration and invasion of NB SH-SY5Y and SiMa cells, further evidenced by the upregulation of human proliferating cell nuclear antigen, Bcl-2, vimentin and fibronectin. Real-time PCR and ELISA results suggested that nanomolar BPA can increase the expression of interleukin-6 (IL-6), but had no effect on the expression of IL-2, IL-8, IL-10 or IL-12. The neutralization antibody of IL-6 can abolish BPA-induced proliferation and invasion of NB cells. The inhibitor of NF-kappa B (BAY 11-7082), but not PD98059 (PD, ERK1/2 inhibitor) or LY294002 (LY, PI3 K/Akt inhibitor), attenuated BPA-induced IL-6 expression and cell proliferation and invasion. In addition, BPA treatment also rapidly increased the phosphorylation of p65 since treatment for 5 min. Collectively, our data revealed that nanomolar BPA can trigger the malignancy of NB cells via activation of NF-kappa B/IL-6 signals, suggesting that more attention should be paid to the potential health risks of daily BPA intake.