Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthetic Polypeptide Derived from Viral Macrophage Inflammatory Protein II Inhibit VEGF Production of Human Glioma U87 Cells through SDF-1α/CXCR4-Mediated AKT Signaling Pathway

Bo Xu, Peng Tian, Gui-Jie An, Sha Liu, Xiu-Ying Li, Han-Xiao Sun , Jing-Gung Zhou, Qing Ding, Pi-Jin Wei

Institute of Genomic Medicine, College of Pharmacy, Jinan University, Guangzhou 510632, China;

For correspondence:- Han-Xiao Sun Email: sunhx718@163.com Tel:+8602038375022

Received: 18 March 2014 Accepted: 3 July 2014 Published: 18 August 2014

Citation: Xu B, Tian P, An G, Liu S, Li X, Sun H, et al. Synthetic Polypeptide Derived from Viral Macrophage Inflammatory Protein II Inhibit VEGF Production of Human Glioma U87 Cells through SDF-1α/CXCR4-Mediated AKT Signaling Pathway. Trop J Pharm Res 2014; 13(8):1327-1332 doi: 10.4314/tjpr.v13i8.18

© 2014 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To evaluate the effect of synthetic polypeptide (N15P) derived from viral macrophage inflammatory protein II (vMIP-II) on the secretion of vascular endothelial growth factor (VEGF) as well as investigate the signaling pathways involved in stromal cell-derived factor-1α (SDF-1α)/CXC Chemokin Receptor 4 (CXCR4) axis-induced VEGF in glioblastoma U87 cells.

Methods: Glioblastoma U87 cells were exposed to SDF-1α, N15P with various concentrations. The expression of CXCR4, SDF-1α and VEGF mRNA were assessed by RT-PCR, while expression level of VEGF was tested by ELISA and protein kinase B (Akt) phosphorylation detected by Western blot.

Results: The results showed that CXCR4, SDF-1α, VEGF are expressed in human glioblastoma U87 cell lines. SDF-1α caused a dose-dependent sensitivity of cell proliferation with a maximum effect at 15 µmole/ml, while N15P decreased cell viability in U87 cells in a dose-dependent manner. SDF-1α stimulated the activation of VEGF, and N15P inhibited the activation of VEGF with or without SDF-1α stimulation. VEGF production in U87 cells was associated with Akt pathway. These changes in intracellular processes were blocked by N15P in a dose-dependent manner.

Conclusion: The results suggest that N15P suppress SDF-1α/CXCR4 Mediated VEGF production through Akt signaling pathway and this may be a potent therapeutic strategy in glioblastoma.

Keywords: Viral macrophage, Inflammatory protein II, Glioblastoma, CXC chemokin receptor 4, Stromal cell-derived factor-1^5;, Protein kinase B