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

研究成果: 雜誌貢獻文章同行評審

35 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1605-1612
頁數8
期刊Child's Nervous System
26
發行號11
DOIs
出版狀態已發佈 - 11月 2010
對外發佈

ASJC Scopus subject areas

  • 兒科、圍產兒和兒童健康
  • 神經病學(臨床)

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