Journal Article

Celecoxib enhances radiosensitivity of hypoxic glioblastoma cells through endoplasmic reticulum stress

Kenshi Suzuki, Ariungerel Gerelchuluun, Zhengshan Hong, Lue Sun, Junko Zenkoh, Takashi Moritake and Koji Tsuboi

in Neuro-Oncology

Published on behalf of Society for Neuro-Oncology

Volume 15, issue 9, pages 1186-1199
Published in print September 2013 | ISSN: 1522-8517
Published online May 2013 | e-ISSN: 1523-5866 | DOI: http://dx.doi.org/10.1093/neuonc/not062
Celecoxib enhances radiosensitivity of hypoxic glioblastoma cells through endoplasmic reticulum stress

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Background

Refractoriness of glioblastoma multiforme (GBM) largely depends on its radioresistance. We investigated the radiosensitizing effects of celecoxib on GBM cell lines under both normoxic and hypoxic conditions.

Methods

Two human GBM cell lines, U87MG and U251MG, and a mouse GBM cell line, GL261, were treated with celecoxib or γ-irradiation either alone or in combination under normoxic and hypoxic conditions. Radiosensitizing effects were analyzed by clonogenic survival assays and cell growth assays and by assessing apoptosis and autophagy. Expression of apoptosis-, autophagy-, and endoplasmic reticulum (ER) stress–related genes was analyzed by immunoblotting.

Results

Celecoxib significantly enhanced the radiosensitivity of GBM cells under both normoxic and hypoxic conditions. In addition, combined treatment with celecoxib and γ-irradiation induced marked autophagy, particularly in hypoxic cells. The mechanism underlying the radiosensitizing effect of celecoxib was determined to be ER stress loading on GBM cells.

Conclusion

Celecoxib enhances the radiosensitivity of GBM cells by a mechanism that is different from cyclooxygenase-2 inhibition. Our results indicate that celecoxib may be a promising radiosensitizing drug for clinical use in patients with GBM.

Keywords: autophagy; celecoxib; ER stress; glioblastoma; hypoxia; radiosensitivity

Journal Article.  6292 words.  Illustrated.

Subjects: Medical Oncology ; Neurology

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