Introduction: All-trans retinoid acid (ATRA) is one of the strongest and most thoroughly studied differentiation inducers that can induce the differentiation and apoptosis of glioma. However, the effects of ATRA on the angiogenesis of glioma remain poorly understood. The present study investigated the effects of ATRA on the expression of Vascular Endothelial Growth Factor (VEGF) and Hypoxia-inducible Factor-1a (HIF-1a) in different glioma cell lines both in normoxia and hypoxia condition and its effects on angiogenesis in rat intracerebral glioma model
Methods: U87 and SHG44 glioma cells were treated by ATRA in different concentrations (0, 5, 10, 20, 40µmol/L) in normoxia or hypoxia condition respectively. Real-time PCR was used to investigate the mRNA expression, Western Blot was used to investigate the protein expression of VEGF and HIF-1a. The intracerebral glioma model was made by intracerebral implantation of C6 glioma Cells into rat. Tumor bearing rat were treated by ATRA in different doses (0, 5mg/Kg/d, 10mg/Kg/d) for two weeks, immunohistochemical assays was used to detect the CD34 positive cells to evaluate the microvessel density (MVD) in each group.
Results: After treated with ATRA, the expression of VEGF and HIF-1a showed the opposite results in different groups. In lower concentration groups (5, 10µmol/L), ATRA could increase the expression of VEGF and HIF-1a remarkably. Conversely, ATRA could significantly down regulated VEGF and HIF-1a expression in high concentration(40µmol/L), compared with that in the contol group. Moreover, ATRA could decrease the MVD of glioma in treated groups, especially in high dose group (10mg/Kg/d) compared to the control group.
Conclusions: ATRA could exert bi-directional regulation effects on expression of VEGF and HIF-1a in glioma cell lines. It may partially related to its concentration. In addition, ATRA could inhibit the angiogenesis of glioma in vivo.
Patient Care: This study could lay the groundwork for clinical research.
Learning Objectives: The conclusions of this study could partially reveal the effects of ATRA on the angiogenesis of glioma.