Ursolic acid inhibits epithelial-mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells.

ABSTRACT

Lung cancer is one of the most death-related cancers worldwide. Ursolic acid (UA), a pentacyclic triterpene acid, has a wide range of anticancer functions such as proapoptosis, antiangiogenesis, and antimetastasis. This study was carried out to explore the inhibition mechanism of UA on metastasis of lung cancer A549 cells. First, we found that UA inhibited the metastasis of lung cancer cells in a concentration-dependent manner through an adhesion assay, a cell wound healing assay, and a transwell migration assay in vitro. In addition, after treatment with UA, the A549 cells showed decreased expression of astrocyte-elevated gene-1 (AEG-1) accompanied by upregulation of E-cadherin and downregulation of N-cadherin and vimentin, which have been reported to characterize the epithelial-mesenchymal transition (EMT). Further results also confirmed that the expression of vimentin was decreased by the siRNA technique to directly knock down AEG-1 expression, indicating that AEG-1 was involved in UA-mediated EMT inhibition. Furthermore, our results showed that UA suppressed the expression level of AEG-1 by repressing nuclear factor-κB signaling. Altogether, UA inhibited the EMT by suppressing the expression of AEG-1, correlating with inhibition of nuclear factor-κB in A549 cells. These findings suggested that UA was a potent anti-lung cancer agent, and it may be able to prevent invasion and metastasis of lung cancer cells.