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Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells

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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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Acknowledgment

This study was supported by research grants from the National Science Council (NSC-98-3111-B-075-001-MY3), Chi Mei Medical Center (CMYM 9801), Taipei Veterans General Hospital (V97E1-008, V97F-001), Yen-Tjing-Ling Medical Foundation (95/96/97/98), Taipei City Hospital (96001-62-014, 96001-62-018, 96002-62-092, and 97001-62-003) and National Yang-Ming University (Ministry of Education, Aim for the Top University Plan), and Technology Development Program for Academia (98-EC-17-A-19-S2-0107), Department of Industrial Technology, Ministry of Economic Affairs, Taiwan.

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Authors and Affiliations

  1. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan

    Chuan-Chih Hsu, Cheng-Deng Kuo & Shih-Hwa Chiou

  2. Cancer Center, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan

    Yi-Wei Chen

  3. Division of Neurosurgery, Department of Surgery, Cheng-Hsin General Hospital, Taipei, Taiwan

    Wen-Shin Song

  4. Department of Medical Research and Education, Cheng-Hsin General Hospital, Taipei, Taiwan

    Chi-Shuan Huang, Chia-Chen Tsai & Kai-Hsi Lu

  5. Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan

    Ching-Yao Tsai & Lin-Chung Woung

  6. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan

    Tung-Hu Tsai, Ching-Yao Tsai & Lin-Chung Woung

  7. Department of Surgery, Chi-Mei Medical Center & Chia Nan University of Pharmacy & Science, Tainan, Taiwan

    Chuan-Chih Hsu

  8. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Kuan-Hsuan Chen, Ching-Yao Tsai, Lin-Chung Woung, Shih-Hwa Chiou & Yi-Wei Chen

  9. Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan

    Cheng-Deng Kuo & Han-Shui Hsu

  10. Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan

    Tung-Hu Tsai

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  1. Kuan-Hsuan Chen
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Corresponding authors

Correspondence to Shih-Hwa Chiou, Kai-Hsi Lu or Yi-Wei Chen.

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Kuan-Hsuan Chen, Chuan-Chih Hsu, and Wen-Shin Song contributed equally to this work.

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Chen, KH., Hsu, CC., Song, WS. et al. Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells. Childs Nerv Syst 26, 1605–1612 (2010). https://doi.org/10.1007/s00381-010-1190-2

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  • DOI: https://doi.org/10.1007/s00381-010-1190-2

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