A stimulating effect induced by Bisphenol A bis (diphenylphosphate) in HepG2 cells via vascular endothelial growth...

With the widespread distribution and increasing detection levels of Bisphenol A bis (diphenylphosphate) (BDP) in environment, toxicity risk assessment on BDP has become indispensable issue. So far, available toxicological information about BDP is still limited. In this study, a hormesis-like effect of BDP in HepG2 cells was observed and potential mechanism was investigated. BDP (<2 μM) promoted proliferation ability and stimulated the migration and invasion ability of HepG2 cells as evidenced by increased viability, accelerated colony formation, hasted scratch healing, down-regulated E-cadherin, and up-regulated matrix metalloproteinase (MMP-9) and mouse double minute 2 homolog (MDM2) proteins. However, high doses of BDP (>20 μM) exhibited completely opposite effects to that of lower dose. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis was involved in the stimulating effect induced by 0.2 μM of BDP through activation of the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway and extracellular regulated protein kinases (ERK)/p38 mitogen activated protein kinase (MAPK) cascades, and there was a bidirectional regulation between the latter two pathways. Our results demonstrated the network of VEGF/VEGFR, Akt/mTOR, and ERK/p38 MAPK pathways involving in BDP-induced stimulating effect on proliferation, migration and invasion ability of HepG2 cells, which providing a novel insight on toxicology risk assessment of BDP.