Actinidia callosa var. callosa suppresses metastatic potential of human hepatoma cell SK-Hep1 by inhibiting matrix metalloproteinase-2 through PI3K/Akt and MAPK signaling pathways

Cancer cell metastasis involving multi-step procedures and cytophysiological property changes may make difficult in the clinical management and death rate increasing. In this study, we first observed that ethyl acetate fraction of Actinidia callosa var. callosa (EAAC) carry out a dose-dependent inhibitory effect without cytotoxicity on the mobility and invasion of highly metastatic SK-Hep1 cells. To investigate the EAAC in cancer metastasis, SK-Hep1 cells were treated with EAAC at various concentrations and then subjected to gelatin zymography, casein zymography and western blot to study the impacts of EAAC on metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1/2 (TIMP-1/2), respectively. Our results showed that EAAC treatment may decrease the expressions of MMP-2 and enhance the expression of TIMP-1/2 in a concentration-dependent manner. EAAC also inhibited effect on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase/serine/threonine protein kinase [or protein kinase B (PI3K/Akt)] and focal adhesion kinase (FAK). These results indicate that EAAC inhibited SK-Hep1 cell of metastasis by reduced protein level of MMP-2 through the suppression of MAPK and FAK signaling pathway and of the activity of PI3K/Akt. These findings suggest that EAAC may be used as an antimetastatic agent.