Resveratrol suppresses serum-induced vasculogenic mimicry through impairing the EphA2/twist-VE-cadherin/AKT pathway in human prostate cancer PC-3 cells

Abstract

Vasculogenic mimicry (VM) is closely related to cancer progression and metastasis, contributing to poor prognosis in patients with cancer. Resveratrol (RES) is well known to possess anti-cancer activity. This study explored the new role of RES in VM incidence in human prostate cancer (PCa) PC-3 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, transwell invasion, and three-dimensional culture VM tube formation assays were performed to check the cell viability, invasive ability, and vessel-like networks formation, respectively. VM-related proteins were detected by Western blots. The activity of metalloproteinase-2 (MMP-2) was identified by gelatin zymography. Vascular endothelial cadherin (VE-cadherin) mRNA was assessed by reverse transcriptase-polymerase chain reaction. Nuclear twist expression was observed by immunofluorescence assay. RES reduced serum-induced invasion and VM formation. Serum-induced phosphorylation of erythropoiethin-producing hepatoceullular A2 (EphA2) and the expression of VE-cadherin at the protein and mRNA levels were decreased after RES treatment. RES inhibited serum-induced expression and nuclear localization of twist. Serum-activated AKT signaling pathway, including MMP-2 and laminin subunit 5 gamma-2, was impaired by RES. These results suggested that RES may have an anti-VM effect through suppressing the EphA2/twist-VE-cadherin/AKT signaling cascade in PCa PC-3 cells.