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Child's Nervous System
Published in: Child's Nervous System 11/2010

01-11-2010 | Original Paper

Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells

Authors: Kuan-Hsuan Chen, Chuan-Chih Hsu, Wen-Shin Song, Chi-Shuan Huang, Chia-Chen Tsai, Cheng-Deng Kuo, Han-Shui Hsu, Tung-Hu Tsai, Ching-Yao Tsai, Lin-Chung Woung, Shih-Hwa Chiou, Kai-Hsi Lu, Yi-Wei Chen

Published in: Child's Nervous System | Issue 11/2010

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Abstract

Objects

Cyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid to prostaglandins, is overexpressed in a variety of tumors, including medulloblastoma (MB). CD133, a transmembrane glycoprotein, has been suggested as a marker for cancer stem cells in brain tumors. The aim of the present study was to investigate the role of celecoxib, a selective COX-2 inhibitor, in enhancing the effects of ionizing radiotherapy (IR) on medulloblastoma-derived CD133-positive cells (MB-CD133+).

Materials and methods

MB-CD133+ were isolated from two medulloblastoma cell lines (Daoy and UW228). Then, they were treated with celecoxib in different concentrations, and cell viability was assessed. The assays of cell survival, soft agar, radiosensitivity, colony formation, and apoptotic activity in MB-CD133+ treated with celecoxib alone, radiation alone, or celecoxib combined with radiation were further evaluated.

Results

MB-CD133+ showed the self-renew ability to form sphere bodies in vitro and regenerate tumors in vivo. The levels of COX-2 mRNA and protein in MB-CD133+ were significantly higher than those in MB-CD133−. The treatment of 30 μM celecoxib could effectively inhibit the abilities of cell proliferation and colony formation and increase IR-induced apoptosis in treated MB-CD133+. Furthermore, in vivo study demonstrated that celecoxib significantly enhanced radiosensitivity in MB-CD133+-transplanted grafts. Notably, xenotransplantation analysis demonstrated that the treatment of celecoxib could further suppress the expressions of angiogenic and stemnness-related genes in treated MB-CD133+ grafts of SCID mice.

Conclusions

Celecoxib presents the potential of radiosensitizing effect in MB-derived cancer stem cells. Therefore, it should be warranted in future trials to enhance the radiotherapeutic effects in MB patients.
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Metadata
Title
Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells
Authors
Kuan-Hsuan Chen
Chuan-Chih Hsu
Wen-Shin Song
Chi-Shuan Huang
Chia-Chen Tsai
Cheng-Deng Kuo
Han-Shui Hsu
Tung-Hu Tsai
Ching-Yao Tsai
Lin-Chung Woung
Shih-Hwa Chiou
Kai-Hsi Lu
Yi-Wei Chen
Publication date
01-11-2010
Publisher
Springer-Verlag
Published in
Child's Nervous System / Issue 11/2010
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-010-1190-2

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