Enhanced radiosensitivity and radiation-induced apoptosis in glioma CD133-positive cells by knockdown of SirT1 expression

Charn Jung Chang, Chuan Chih Hsu, Ming Chi Yung, Kai Yun Chen, Ching Tzao, Wei Fong Wu, Hsiang Yun Chou, Yi Yen Lee, Kai Hsi Lu, Shih Hwa Chiou, Hsin I. Ma

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

CD133-expressing glioma cells play a critical role in tumor recovery after treatment and are resistant to radiotherapy. Herein, we demonstrated that glioblastoma-derived CD133-positive cells (GBM-CD133+) are capable of self-renewal and express high levels of embryonic stem cell genes and SirT1 compared to GBM-CD133- cells. To evaluate the role of SirT1 in GBM-CD133+, we used a lentiviral vector expressing shRNA to knock-down SirT1 expression (sh-SirT1) in GBM-CD133+. Silencing of SirT1 significantly enhanced the sensitivity of GBM-CD133+ to radiation and increased the level of radiation-mediated apoptosis. Importantly, knock-down of SirT1 increased the effectiveness of radiotherapy in the inhibition of tumor growth in nude mice transplanted with GBM-CD133+. Kaplan-Meier survival analysis indicated that the mean survival rate of GBM-CD133+ mice treated with radiotherapy was significantly improved by Sh-SirT1 as well. In sum, these results suggest that SirT1 is a potential target for increasing the sensitivity of GBM and glioblastoma-associated cancer stem cells to radiotherapy.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume380
Issue number2
DOIs
Publication statusPublished - Mar 6 2009
Externally publishedYes

Keywords

  • CD133
  • Glioblastoma
  • Radiotherapy
  • SirT1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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