Abstract 3025: HER2/Stat3 signaling mediated radioresistance in U87 glioma cancer cells through suppressed apoptosis and enhanced glycolysis

Abstract

Abstract GBM is the most common and aggressive malignant primary brain tumor, and the prognosis for GBM patients remains poor. Radiotherapy continues to play a central role in the management of brain tumors. Even though the advances of radiotherapy strategies and techniques, frequent failure of radiotherapy made GBM a disease difficult to be treated. GBM cancer stem cells (CSCs) are reported to be responsible for resistance to chemo- and radiotherapy, and chemotherapy and radiotherapy resistant GBM CSCs have been isolated from GBM. However, the mechanisms of radioresistance of glioma cells are still elucidative. In this study, we investigated the role of HER2-Stat3 signaling pathway in radioresistance using human glioma cell line U87. We found that long-term therapeutic dose of fragmented irradiation induces repopulation of human glioma U87 cells with increased number of CD133+/HER2+ stem-like cells. FIR-surviving CD133+/HER2+ U87 cells have coactivation of HER2 and Stat3 and increased cell proliferation and invasion abilities. More importantly, we found that U87-FIR cells have lower level of mitochondria metabolism and ROS level, and higher mitochondrial membrane potential, while 5Gy single dose radiation induces increased mitochondria function. Furthermore, U87 cell injection derived xenograph tumor also has increased mitochondrial membrane potential and decreased mitochondria function after radiation. These results suggest that the radioresistance of GBM CSCs possibly due to the suppressed apoptosis and enhanced glycolysis mediated by HER2/STAT3 pathway. Citation Format: Lili Qin, Ming Fan, Jian Jian Li. HER2/Stat3 signaling mediated radioresistance in U87 glioma cancer cells through suppressed apoptosis and enhanced glycolysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3025. doi:10.1158/1538-7445.AM2014-3025