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Synergistic effect of TRAIL and irradiation in elimination of glioblastoma stem-like cells
Authors:Junfeng Liu  Qinglei Gao  Tao Xie  Yu Liu  Longjun Luo  Cheng Xu  Lu Shen  Feng Wan  Ting Lei  Fei Ye
Affiliation:1.Department of Neurosurgery, Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology,Wuhan,People’s Republic of China;2.Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology,Wuhan,People’s Republic of China;3.Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College,Huazhong University of Science and Technology,Wuhan,People’s Republic of China
Abstract:Glioblastoma multiforme (GBM) is the most common malignancy in central nervous system. A small subpopulation of GBM cells known as GBM stem-like cells (GSLCs) were supposed to be the most malignant cells among GBM cells as they are resistant to multiple therapies including radiotherapy. In this study, we set up two GSLCs cell lines from the two parental U87 and U251 glioma cell lines, and studied the expression of apoptosis-related genes alteration in GSLCs before and after irradiation. We found that one of the receptors of TNF-related apoptosis-inducing ligand (TRAIL), DR5, was dramatically up-regulated in GSLCs after irradiation (IR). Although GSLCs are resistant to both TRAIL and radiation treatment alone, the combined treatment with TRAIL and irradiation achieved maximum killing effect of GSLCs due to inducing the expression of DR5 and inhibiting the expression of cFLIP. Therefore, TRAIL and IR combined treatment would be a simple but practical therapeutic strategy for clinical application.
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