Sotetsuflavone suppresses invasion and metastasis in non-small-cell lung cancer A549 cells by reversing EMT via the TNF-α/NF-κB and PI3K/AKT signaling pathway

Abstract

, which has excellent anticancer activity in the early stages. The present study aims to evaluate the anti-metastatic potential of sotetsuflavone in vitro. Our data demonstrated that sotetsuflavone inhibits metastasis of A549 cells, and EMT. This inhibition was reflected in the upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, and Snail. Mechanistically, our study demonstrated that HIF-1α played an important role in the anti-metastatic effect of sotetsuflavone in non-small-cell lung cancer A549 cells. Sotetsuflavone not only mediated VEGF expression but also downregulated VEGF and upregulated angiostatin, and simultaneously affected the expression of MMPs and decreased MMP-9 and MMP-13 expression. More importantly, HIF-1α expression may be regulated by the inhibition of PI3K/AKT and TNF-α/NF-κB pathways. These results suggest that sotetsuflavone can reverse EMT, thereby inhibiting the migration and invasion of A549 cells. This process may be associated with both PI3K/AKT and TNF-α/NF-κB pathways, and sotetsuflavone may be efficacious in the treatment of non-small-cell lung cancer.