Dr. Senckenberg Institute of Neurooncology and University Cancer Center (UCT), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany.
German Cancer Research Center (DKFZ) Heidelberg, and German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, 60590 Frankfurt am Main, Germany.
Int J Mol Sci. 2019 Mar 1;20(5):1061. doi: 10.3390/ijms20051061.
The TP53-induced glycolysis and apoptosis regulator (TIGAR) has been shown to decrease glycolysis, to activate the pentose phosphate pathway, and to provide protection against oxidative damage. Hypoxic regions are considered characteristic of glioblastoma and linked with resistance to current treatment strategies. Here, we established that LNT-229 glioma cell lines stably expressed shRNA constructs targeting , and exposed them to hypoxia, irradiation and temozolomide. The disruption of enhanced levels of reactive oxygen species and cell death under hypoxic conditions, as well as the effectiveness of irradiation and temozolomide. In addition, was upregulated by HIF-1α. As a component of a complex network, TIGAR contributes to the metabolic adjustments that arise from either spontaneous or therapy-induced changes in tumor microenvironment.
TP53 诱导的糖酵解和凋亡调节剂(TIGAR)已被证明可以降低糖酵解,激活磷酸戊糖途径,并提供对抗氧化损伤的保护。缺氧区域被认为是胶质母细胞瘤的特征,并与当前治疗策略的耐药性有关。在这里,我们建立了稳定表达靶向 shRNA 构建体的 LNT-229 神经胶质瘤细胞系,并将其暴露于缺氧、辐射和替莫唑胺下。破坏 在缺氧条件下增强了活性氧和细胞死亡的水平,以及辐射和替莫唑胺的有效性。此外,HIF-1α 上调了 。作为一个复杂网络的组成部分,TIGAR 有助于肿瘤微环境中自发或治疗诱导的变化所产生的代谢调整。