Knockdown of the TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Sensitizes Glioma Cells to Hypoxia, Irradiation and Temozolomide

International Journal of Molecular Sciences

GabrieleD. Maurer¹  JoachimP. Steinbach¹  Christina Wanka¹  Johannes Rieger¹  Sonja Heller¹ 

[1] Dr. Senckenberg Institute of Neurooncology and University Cancer Center (UCT), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany;

关键词: TP53-induced glycolysis and apoptosis regulator;    glioma;    hypoxia;    irradiation;    temozolomide;    reactive oxygen species;    hypoxia-inducible factor;   

DOI  :  10.3390/ijms20051061

来源: DOAJ

【 摘 要 】

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 TIGAR, and exposed them to hypoxia, irradiation and temozolomide. The disruption of TIGAR enhanced levels of reactive oxygen species and cell death under hypoxic conditions, as well as the effectiveness of irradiation and temozolomide. In addition, TIGAR 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.

【 授权许可】

Unknown