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-1α, Protein
kinase B