Cell cycle progression in glioblastoma cells is unaffected by pathophysiological levels of hypoxia

PeerJ

article

Rosalie Richards¹  Michael D. Jenkinson²  Brian J. Haylock³  Violaine See¹ 

[1] Institute of Integrative Biology, Department of Biochemistry, University of Liverpool;Institute of Translational Medicine, Clinical Science Centre, University of Liverpool;Department of Clinical Oncology, Clatterbridge Cancer Centre

关键词: Hypoxia;    Cell cycle;    HIF;    Glioblastoma;    Cell death;    Tumour microenvironment;    Brain tumours;   

DOI  :  10.7717/peerj.1755

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Hypoxia is associated with the increased malignancy of a broad range of solid tumours. While very severe hypoxia has been widely shown to induce cell cycle arrest, the impact of pathophysiological hypoxia on tumour cell proliferation is poorly understood. The aim of this study was to investigate the effect of different oxygen levels on glioblastoma (GBM) cell proliferation and survival. GBM is an extremely aggressive brain tumour with a heterogeneous oxygenation pattern. The effects of a range of oxygen tensions on GBM cell lines and primary cells were assessed using flow cytometry. Results indicate that cell cycle distribution and viability are unaffected by long term exposure (24–96 h) to pathophysiological levels of oxygen (1–8% O2). Both transient cell cycle arrest and small amounts of cell death could only be detected when cells were exposed to severe hypoxia (0.1% O2). No significant changes in p21 protein expression levels were detected. These findings reinforce the importance of using physiologically relevant oxygen tensions when investigating tumour hypoxia, and help to explain how solid tumours can be both hypoxic and highly proliferative, as is the case with GBM.

【 授权许可】

CC BY