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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1605-1612
Number of pages8
JournalChild's Nervous System
Volume26
Issue number11
DOIs
Publication statusPublished - Nov 2010
Externally publishedYes

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Celecoxib
Medulloblastoma
Radiation Tolerance
Neoplastic Stem Cells
Cyclooxygenase 2
Cell Survival
Radiotherapy

Keywords

  • CD133
  • Celecoxib
  • Daoy
  • Medulloblastoma
  • Radiosensitivity

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Chen, K. H., Hsu, C. C., Song, W. S., Huang, C. S., Tsai, C. C., Kuo, C. D., ... Chen, Y. W. (2010). Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells. Child's Nervous System, 26(11), 1605-1612. https://doi.org/10.1007/s00381-010-1190-2

Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells. / Chen, Kuan Hsuan; Hsu, Chuan Chih; Song, Wen Shin; Huang, Chi Shuan; Tsai, Chia Chen; Kuo, Cheng Deng; Hsu, Han Shui; Tsai, Tung Hu; Tsai, Ching Yao; Woung, Lin Chung; Chiou, Shih Hwa; Lu, Kai Hsi; Chen, Yi Wei.

In: Child's Nervous System, Vol. 26, No. 11, 11.2010, p. 1605-1612.

Research output: Contribution to journalArticle

Chen, KH, Hsu, CC, Song, WS, Huang, CS, Tsai, CC, Kuo, CD, Hsu, HS, Tsai, TH, Tsai, CY, Woung, LC, Chiou, SH, Lu, KH & Chen, YW 2010, 'Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells', Child's Nervous System, vol. 26, no. 11, pp. 1605-1612. https://doi.org/10.1007/s00381-010-1190-2
Chen, Kuan Hsuan ; Hsu, Chuan Chih ; Song, Wen Shin ; Huang, Chi Shuan ; Tsai, Chia Chen ; Kuo, Cheng Deng ; Hsu, Han Shui ; Tsai, Tung Hu ; Tsai, Ching Yao ; Woung, Lin Chung ; Chiou, Shih Hwa ; Lu, Kai Hsi ; Chen, Yi Wei. / Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells. In: Child's Nervous System. 2010 ; Vol. 26, No. 11. pp. 1605-1612.
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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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AU - Tsai, Chia Chen

AU - Kuo, Cheng Deng

AU - Hsu, Han Shui

AU - Tsai, Tung Hu

AU - Tsai, Ching Yao

AU - Woung, Lin Chung

AU - Chiou, Shih Hwa

AU - Lu, Kai Hsi

AU - Chen, Yi Wei

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