Anti-angiogenetic therapy for malignant brain tumor

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: OITA MEDICAL UNIVERSITY
• Principal Investigator: MORI Teruaki Oita Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60124632)
• Project Period (FY): 1999 – 2000
• Keywords: Glioma / NF_κB / I_κB / Gene therapy / Angiogenesis

Research Abstract

Recent studies have demonstrated that pleiotropic transcription factor NF-κB/relA plays an important role in the control of cell proliferation and apoptosis and hence oncogenesis. Different neoplasma have been shown to express high levels of NF-κB/relA. In this study, we investigated effects of inhibitor of NF-κB(IκB) on angiogenesis of human glioma cells. For this purpose, the human glioblastoma multiforme-derived cell line (U251) cells were transfected with IκBα(IκBαW) and mutant IκBα(IκBαM), resistant to phosphorylation and degradation, and hence blocks NF-κB activity. NF-κB signaling blocked significantly inhibited in vitro and in vivo expression of the major proangiogenic molecule, vascular endothelial growth factor (VEGF) and other factors, in cultured cells and in cells xenograft in the brain of Wister rat. The decreased expression of vascular growth factors directly correlated with decreased transcription levels of NF-κB, decreased tumorigenicity and vascularization. These finding suggest that inhibition of NF-κB/relA activity in glioma cells can suppress angiogenesis, so it can be a new therapy modalities for glioma to inhibit NF-κB's activity by IκB in the future.