JSI-124 suppresses invasion and angiogenesis of glioblastoma cells in vitro

PloS One
Guang YuanGang Li

Abstract

Glioblastoma multiforme (GBM) is one of the utmost malignant tumors. Excessive angiogenesis and invasiveness are the major reasons for their uncontrolled growth and resistance toward conventional strategies resulting in poor prognosis. In this study, we found that low-dose JSI-124 reduced invasiveness and tumorigenicity of GBM cells. JSI-124 effectively inhibited VEGF expression in GBM cells. In a coculture study, JSI-124 completely prevented U87MG cell-mediated capillary formation of HUVECs and the migration of HUVECs when cultured alone or cocultured with U87MG cells. Furthermore, JSI-124 inhibited VEGF-induced cell proliferation, motility, invasion and the formation of capillary-like structures in HUVECs in a dose-dependent manner. JSI-124 suppressed VEGF-induced p-VEGFR2 activity through STAT3 signaling cascade in HUVECs. Immunohistochemistry analysis showed that the expression of CD34, Ki67, p-STAT3 and p-VEGFR2 protein in xenografts was remarkably decreased. Taken together, our findings provide the first evidence that JSI-124 effectively inhibits tumor angiogenesis and invasion, which might be a viable drug in anti-angiogenesis and anti-invasion therapies.

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Citations

Sep 24, 2016·Molecular Neurobiology·Zangbéwendé Guy OuédraogoEmmanuel Chautard
Jun 10, 2017·Journal of Neuro-oncology·Yu QinMadhuri Wadehra
Dec 19, 2016·Biochemical and Biophysical Research Communications·Lulu CuiXiaochun Wan
Jun 18, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Kong-Liang LiHong-Yu Yang

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Methods Mentioned

BETA
electrophoresis
Enzyme-Linked
ELISA
flow cytometry
xenograft
flow
xenografts

Software Mentioned

Pro Plus
Image

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