Abstract
Epithelial-mesenchymal transition (EMT) is associated with tumor invasion and metastasis, and offers insight into novel strategies for cancer treatment. Sotetsuflavone was isolated from Cycas revolute, 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.
Highlights
Lung cancer is a malignant tumor with the highest morbidity and mortality worldwide, with 1.38 million new cases each year, and over one million deaths worldwide annually[1]
Sotetsuflavone inhibited Epithelial-mesenchymal transition (EMT) in A549 cells Sotetsuflavone significantly upregulated the expression of E-cadherin, and downregulated the expression of Ncadherin, vimentin, and snail, thereby inducing mesenchymal-epithelial transition (MET) (Fig. 2a–c)
The results demonstrated that sotetsuflavone could inhibit the migration and invasion of A549 cells by reversing EMT
Summary
Lung cancer is a malignant tumor with the highest morbidity and mortality worldwide, with 1.38 million new cases each year, and over one million deaths worldwide annually[1]. Non-small-cell lung cancer (NSCLC) accounts for 80–85% of lung cancers, with a 5-year survival rate of
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