Salvianolic acid B acts against non-small cell lung cancer A549 cells via inactivation of the MAPK and Smad2/3 signaling pathways

Abstract

Salvianolic acid B (Sal B) is a potential cytotoxic polyphenol against cancer. In the present study the effect of Sal B and its molecular mechanism were investigated in the non-small cell lung cancer (NSCLC) A549 cell line. The TGF-β/MAPK/Smad signaling axis was explored. A549 cells were co-cultured with and without different concentrations of Sal B (25, 50 and 100 μM respectively) and TGF-β1 (9 pM) for 24 h. Cell epithelial-mesenchymal transition (EMT), cell migration, cell cycle distribution, autophagy and apoptosis were assessed by western blotting (WB), wound healing assay and flow cytometry, respectively. Moreover, activation of MAPK, Smad2/3 and the downstream target, plasminogen activator inhibitor 1 (PAI-1), were assessed by WB. The results demonstrated that Sal B inhibited TGF-β1-induced EMT and migration of A549 cells, hampered cell cycle progression and induced cell autophagy and apoptosis. Furthermore, Sal B inactivated MAPK signaling pathways and the phosphoryla- tion of Smad2/3, especially the phosphorylation of Smad3 at the linker region, which resulted in decreased protein expres- sion levels of PAI-1 in TGF-β1-stimulated A549 cells. Overall, these results demonstrated that Sal B may have a potential therapeutic effect against NSCLC in vitro. The results of the present study indicated that the underlying active mechanism of Sal B in NSCLC may be closely related to the impeded activation of the MAPK and Smad2/3 signaling pathways. Therefore, Sal B may be a potential candidate NSCLC thera- peutic agent.