Differential downregulation of vascular endothelial growth factor by dexamethasone in normoxic and hypoxic rat glioma cells

Machein; Kullmer; Rönicke; Machein; Krieg; Damert; Breier; Risau; Plate

doi:10.1046/j.1365-2990.1999.00166.x

Cited by 113Angiogenesis and VEGF in CancerGlioma Diagnosis and TreatmentCancer, Hypoxia, and Metabolism

Differential downregulation of vascular endothelial growth factor by dexamethasone in normoxic and hypoxic rat glioma cells

Machein, Kullmer, Rönicke, Machein, Krieg, Damert, Breier, Risau +1 more·1999·Neuropathology and Applied Neurobiology

DOI 10.1046/j.1365-2990.1999.00166.x

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Abstract

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is a mitogen and chemotactic factor for endothelial cells in vitro and an angiogenesis and vascular permeability factor in vivo. Due to its properties, VEGF is a candidate for both angiogenesis and vascular permeability/oedema induction which typically occur in glioblastomas. In this study we test the hypothesis that the antioedema effect of dexamethasone is mediated by downregulation of VEGF or VEGF receptor expression. VEGF mRNA and protein levels of two rat glioma cells lines, C6 and GS‐9L, were determined after incubation with dexamethasone under normoxic and hypoxic conditions. In normoxic C6 and GS9L cells, we observed 50–60% downregulation of VEGF mRNA by dexamethasone (P=0.015 and P=0.01, respectively). This effect was dependent on glucocorticoid‐receptor (GR) function. The inhibitory effect of dexamethasone on VEGF gene expression by tumour cells was markedly reduced by hypoxia which suggests that the upregulation of VEGF driven by hypoxia overcomes the effect of the dexamethasone. Dexamethasone did not alter VEGFR‐2 mRNA levels in human umbilical endothelial cells. In a subcutaneous glioma tumour model, we observed only a 15% decrease in VEGF mRNA expression in dexamethasone treated animals (n=12) compared with controls animals (P=0.24). We conclude that dexamethasone may decrease brain tumour‐associated oedema by reduction of VEGF expression in tumour cells. However, the highly reduced activity on hypoxic tumour cells suggests that dexamethasone efficacy may be limited by hypoxia in rapidly growing tumours.

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Glucocorticoids including dexamethasone have been shown to decrease the in vivo activity of VEGF.
“glucocorticoids including DX have been shown to decrease the in vivo activity of VEGF.207–209”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [208]

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Authors: Machein, Kullmer, Rönicke, Machein, Krieg, Damert, Breier, Risau, & Plate
Corresponding author: Plate
Venue: Neuropathology and Applied Neurobiology
Publisher: Wiley
Published: 1999-04
Volume: 25
Issue: 2
Pages: 104-112
ISSN: 0305-1846 (ISSN-L)
1365-2990
DOI: 10.1046/j.1365-2990.1999.00166.x
OpenAlex: W2133286797
Cited by: 113
References: 37
Citations by year: 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 5 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 4
FWCI: 1.38
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1009 d)
Locations: Neuropathology and Applied Neurobiology (publishedVersion)
PubMed (publishedVersion)
FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords: vascular endothelial growth factor, dexamethasone, glioma, hypoxia, glucocorticoid receptor, VEGF receptor 2, angiogenesis, VEGF expression, C6 cells
MeSH terms: Animals, Cell Line, Dexamethasone, Endothelium, Vascular, Estradiol, Glioma, Glucocorticoids, Humans, Lymphokines, Progesterone, RNA, Messenger, Tumor Cells, Cultured, Umbilical Veins, Down-Regulation, Cell Hypoxia, Endothelial Growth Factors, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Rats

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Differential downregulation of vascular endothelial growth factor by dexamethasone in normoxic and hypoxic rat glioma cells

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