All-trans retinoic acid upregulates VEGF expression in glioma cells in vitro

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 mu mol/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-1 alpha (HIF-1 alpha) mRNA expression was analyzed by using real-time RT-PCR. After treatment with 5 and 10 mu mol/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-1 alpha mRNA expression also increased. ATRA increases the expression of VEGF in glioma cells at both transcriptional and translational levels.