Exposure to hypoxia following irradiation increases radioresistance in prostate cancer cells

Background: Tumor hypoxia is a common feature of prostate tumors associated with the stabilization of hypoxia-inducible-factor 1alpha (HIF-1 alpha) and poor prognosis following radiation therapy. Lack of oxygen at the time of irradiation is associated with radioresistance, but recent reports suggest radioresponse is also modulated by the dynamic nature of tumor hypoxia. Objective: We proposed to evaluate the effect of post-irradiation hypoxic exposure on the radioresponse of 2 prostate cancer (CaP) cell lines (22Rv1, DU145) and to examine whether it correlates with modified cellular responses induced by hypoxia. Methods and results: Aerobic and hypoxic CaP cells exposed to hypoxia (24 h) after irradiation (4 Gy) gained a survival advantage compared with cells fully oxygenated after irradiation. This survival advantage was associated with induction of a G(2)/M cell cycle arrest, reduced induction of apoptosis and decreased amount of senescent cells. These modified cellular responses appeared mediated by HIF-1 alpha. Conclusion: Our data suggest that targeting hypoxia after irradiation may benefit patients with aggressive hypoxic prostate tumors. (C) 2013 Elsevier Inc. All rights reserved.