Inhibition of cell migration by ouabain in the A549 human lung cancer cell line

The Na(+)/K(+)-ATPase α subunit is highly expressed in malignant cells. Ouabain, a cardioactive glycoside, binds to the Na(+)/K(+)-ATPase α subunit and inhibits the activity of Na(+)/K(+)-ATPase. In the present study, the effect of ouabain on the migration of A549 cells was analyzed using the wound healing and transwell chamber migration assays. The impact of ouabain on the expression of E-cadherin, N-cadherin, vimentin, matrix metalloprotease (MMP)-2 and MMP-9 was also evaluated. Ouabain treatment not only inhibited the epidermal growth factor (EGF)-enhanced migration of A549 cells, but also inhibited the basal migration of A549 cells in the absence of EGF. Ouabain decreased the overexpression of N-cadherin and vimentin induced by EGF, and decreased the expression of MMP-2 and -9 in the presence or absence of EGF. Na(+)/K(+)-ATPase is a potent therapeutic target in lung cancer and these observations indicated that the Na(+)/K(+)-ATPase inhibitor, ouabain, retards the invasion of lung cancer cells.