Eupolyphaga sinensis Walker demonstrates angiogenic activity and inhibits A549 cell growth by targeting the KDR signaling pathway

Abstract

Eupolyphaga sinensis Walker has been reported to have anticoagulation, antithrombotic, liver protective and antitumor effects. In the present study, the inhibitory effects on proliferation of A549 human non-small cell lung cancer cells and the underlying mechanisms were examined. Firstly, three solvents, 70% ethanol, distilled water and 95% ethanol, were used to extract Eupolyphaga sinensis Walker. The MTT assay results demonstrated that the 70% ethanol extract more potently reduced the growth of A549 cells and it was therefore adopted in the subsequent experiments. Eupolyphaga sinensis Walker 70% ethanol extract significantly inhibited A549 cell migration in a time- and dose-dependent manner and inhibited human umbilical vein endothelial cell proliferation, migration and tube formation. Furthermore, Eupolyphaga sinensis Walker 70% ethanol extract effectively inhibited blood vessel formation in the established tissue model for angiogenesis. In addition, Eupolyphaga sinensis Walker 70% ethanol extract was demonstrated to inhibit the autophosphorylation of KDR, and downregulate the subsequent activation of AKT and extracellular signal regulated kinase (ERK)1/2 in A549 cells. In conclusion, these findings demonstrated that the antitumor mechanism of Eupolyphaga sinensis Walker 70% ethanol extract was through inhibiting angiogenesis. It functioned by interrupting the autophosphorylation of KDR and subsequently, AKT and ERK1/2.