Child's Nervous System

, Volume 26, Issue 11, pp 1605–1612

Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells

  • 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
Original Paper

DOI: 10.1007/s00381-010-1190-2

Cite this article as:
Chen, K., Hsu, C., Song, W. et al. Childs Nerv Syst (2010) 26: 1605. doi:10.1007/s00381-010-1190-2

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.

Keywords

CelecoxibMedulloblastomaRadiosensitivityDaoyCD133

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Kuan-Hsuan Chen
    • 8
  • Chuan-Chih Hsu
    • 1
    • 7
  • Wen-Shin Song
    • 3
  • Chi-Shuan Huang
    • 4
  • Chia-Chen Tsai
    • 4
  • Cheng-Deng Kuo
    • 1
    • 9
  • Han-Shui Hsu
    • 9
  • Tung-Hu Tsai
    • 6
    • 10
  • Ching-Yao Tsai
    • 5
    • 6
    • 8
  • Lin-Chung Woung
    • 5
    • 6
    • 8
  • Shih-Hwa Chiou
    • 1
    • 8
  • Kai-Hsi Lu
    • 4
  • Yi-Wei Chen
    • 2
    • 8
  1. 1.Department of Medical Research and EducationTaipei Veterans General HospitalTaipeiTaiwan
  2. 2.Cancer CenterTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.Division of Neurosurgery, Department of SurgeryCheng-Hsin General HospitalTaipeiTaiwan
  4. 4.Department of Medical Research and EducationCheng-Hsin General HospitalTaipeiTaiwan
  5. 5.Department of OphthalmologyTaipei City HospitalTaipeiTaiwan
  6. 6.Department of Education and ResearchTaipei City HospitalTaipeiTaiwan
  7. 7.Department of SurgeryChi-Mei Medical Center & Chia Nan University of Pharmacy & ScienceTainanTaiwan
  8. 8.Institute of Clinical MedicineNational Yang-Ming UniversityTaipeiTaiwan
  9. 9.Institute of Emergency and Critical Care MedicineNational Yang-Ming UniversityTaipeiTaiwan
  10. 10.Institute of Traditional MedicineNational Yang-Ming UniversityTaipeiTaiwan