Abstract
All-trans retinoid acid (ATRA) is one of the most potent and most thoroughly studied differentiation inducers that induce the differentiation and apoptosis of glioma cells. However, the effect of ATRA on angiogenesis of glioma remains poorly understood. We examined the effect of ATRA on the expression of vascular endothelial growth factor (VEGF) in different glioma cell lines and investigated the underlying mechanism, intending to partially reveal the effects of ATRA on angiogenesis of glioma. Glioma cells were treated by ATRA at 5 and 10 µmol/L. The VEGF mRNA transcript levels were determined by real-time RT-PCR and the protein levels of VEGF in glioma cells were evaluated by Western blotting assays. Moreover, hypoxia-inducible factor-1α (HIF-1α) mRNA expression was analyzed by using real-time RT-PCR. After treatment with 5 and 10 µmol/L ATRA, the VEGF mRNA transcript levels in glioma cells increased remarkably, compared with that in the control group, and the relative protein expression of VEGF was also up-regulated. Meanwhile, the HIF-1α mRNA expression also increased. ATRA increases the expression of VEGF in glioma cells at both transcriptional and translational levels.
Highlights
Despite the use of the best therapeutic regimens available, the prognosis of malignant glioma, the most common form of primary brain tumors, remains unsatisfactory
We found that compared to the control cells, the vascular endothelial growth factor (VEGF) mRNA transcript levels were significantly upregulated in the two glioma cell lines treated with All-trans retinoic acid (ATRA)
Since VEGF is well known to be regulated by HIF1α, the effect of ATRA on hypoxia-inducible factor-1α (HIF-1α) mRNA transcription in glioma cells was examined by real-time PCR
Summary
Despite the use of the best therapeutic regimens available, the prognosis of malignant glioma, the most common form of primary brain tumors, remains unsatisfactory. We examined ATRA effects on angiogenesis by detecting the expression of the vascular endothelial growth factor (VEGF) gene in two different glioma cell lines U87 and SHG44. ATRA induces VEGF mRNA transcription in glioma cells We treated the glioma cells with different concentrations of ATRA for 24 hours and examined the VEGF mRNA transcript levels by real-time RT-PCR.
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