Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Oncol Rep. 2010 Mar;23(3):725-32.
Angiogenesis is a key pathologic feature of glioblastoma, which is the most common and most lethal primary brain tumor in adults. The degree of angiogenesis has been shown to be inversely related to patient survival. However, the molecular changes leading to angiogenesis in glioblastoma remain poorly understood. In the present study, we found a direct correlation between nuclear factor (NF)-kappaB activation and angiogenesis in glioblastomas. Blockade of NF-kappaB signaling significantly inhibited glioblastoma growth and angiogenesis in nude mice. These effects were consistent with significant inhibition of the expression of multiple angiogenic molecules, including vascular endothelial growth factor, and interleukin-8, in vitro and in vivo. Furthermore, blockade of NF-kappaB signaling also significantly inhibited the angiogenic potential of glioblastoma cells in vitro and angiogenesis of brain tumors in mouse xenograft models. Collectively, these results suggest that NF-kappaB activation plays a critical role in the growth and progression of glioblastoma and is a potential target for therapy for human glioblastoma.
血管生成是神经胶质瘤的一个关键病理特征，神经胶质瘤是成人中最常见和最致命的原发性脑肿瘤。血管生成的程度与患者的生存呈负相关。然而，导致神经胶质瘤血管生成的分子变化仍知之甚少。在本研究中，我们发现核因子（NF）-kappaB 激活与神经胶质瘤中的血管生成之间存在直接相关性。NF-kappaB 信号通路的阻断显著抑制了裸鼠中神经胶质瘤的生长和血管生成。这些效应与体外和体内多种血管生成分子（包括血管内皮生长因子和白细胞介素-8）表达的显著抑制一致。此外，NF-kappaB 信号通路的阻断也显著抑制了神经胶质瘤细胞在体外的血管生成潜能和小鼠异种移植模型中脑肿瘤的血管生成。总之，这些结果表明 NF-kappaB 激活在神经胶质瘤的生长和进展中起着关键作用，是治疗人类神经胶质瘤的潜在靶点。
