Author:
Han Deok-Soo,Lee Hyo-Jeong,Lee Eun-Ok
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.
Funder
National Research Foundation of Korea (NRF) grant funded by the Ministry of Education
National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT
Publisher
Springer Science and Business Media LLC
Reference50 articles.
1. Woodhouse, E. C., Chuaqui, R. F. & Liotta, L. General mechanisms of metastasis. Cancer 80(8 Suppl), 1529–1537 (1997).
2. Carmeliet, P. & Jain, R. K. Angiogenesis in cancer and other diseases. Nature 407(6801), 249–257 (2000).
3. Folkman, J. & Cotran, R. Relation of vascular proliferation to tumor growth. Int. Rev. Exp. Pathol. 16, 207–248 (1976).
4. Folberg, R., Hendrix, M. J. & Maniotis, A. J. Vasculogenic mimicry and tumor angiogenesis. Am J Pathol. 156(2), 361–381 (2000).
5. Vasudev, N. S. & Reynolds, A. R. Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions. Angiogenesis 17(3), 471–494 (2014).
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献