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Biochem Biophys Res Commun. 2009 Mar 6;380(2):236-42. doi: 10.1016/j.bbrc.2009.01.040. Epub 2009 Jan 21.

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

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  • 1Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

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.

PMID:
19166820
[PubMed - indexed for MEDLINE]
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