Resveratrol suppresses serum-induced vasculogenic mimicry through impairing the EphA2/twist-VE-cadherin/AKT pathway in human prostate cancer PC-3 cells
Deok-Soo Han, Hyo‐Jeong Lee, Eun‐Ok Lee
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.