nadph oxidase subunit 4-mediated reactive oxygen species contribute to cycling hypoxia-promoted tumor progression in glioblastoma multiformenadph氧化酶亚基4-mediated活性氧导致自行车hypoxia-promoted多形性成胶质细胞瘤肿瘤恶化.pdfVIP

NADPH Oxidase Subunit 4-Mediated Reactive Oxygen Species Contribute to Cycling Hypoxia-Promoted Tumor Progression in Glioblastoma Multiforme 1 2 3 4 5 Chia-Hung Hsieh *, Woei-Cherng Shyu , Chien-Yi Chiang , Jung-Wen Kuo , Wu-Chung Shen , Ren-Shyan Liu4,6 1 Graduate Institute of Basic Medical Science, China Medical University and Hospital, Taichung, Taiwan, 2 Department of Neurology, Center for Neuropsychiatry, and Graduate Institute of Immunology, China Medical University and Hospital, Taichung, Taiwan, 3 Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, 4 Department of Nuclear Medicine, School of Medicine, School of Biomedical Science and Engineering, National Yang Ming University, Taipei, Taiwan, 5 Department of Radiology, China Medical University and Hospital, Taichung, Taiwan, 6 National PET/Cyclotron Center, Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Abstract Background: Cycling and chronic tumor hypoxia are involved in tumor development and growth. However, the impact of cycling hypoxia and its molecular mechanism on glioblastoma multiforme (GBM) progression remain unclear. Methodology: Glioblastoma cell lines, GBM8401 and U87, and their xenografts were exposed to cycling hypoxic stress in vitro and in vivo. Reactive oxygen species (ROS) production in glioblastoma cells and xenografts was assayed by in vitro ROS analysis and in vivo molecular imaging studies. NADPH oxidase subunit 4 (Nox4) RNAi-knockdown technology was utilized to study the role of Nox4 in cycling hypoxia-mediated ROS production and tumor progression. Furthermore, glioblastoma cells were stably transfected with a retroviral vector bearing a dual reporter gene cassette that allowed for