CD133-positive cells (CD133+) in glioma present the crucial role in the tumor grading, tumorigenicity, and radioresistance. However, the gene regulation mechanisms in maintaining the self-renewal and drug-resistant properties in cancer stem cells (CSC) of glioma are still unclear. SIRT1, is a NAD+ dependent histone deacetylase, regulates the lifespan and aging effect. Some studies revealed the relationship between the tumor control, anti-apoptosis, and anti-angiogenesis by inhibition of SIRT1. In this study, we detected the high expression levels of SirT1 in glioblastoma-derived CD133-positive cells (GBM-CD133+) as compared to GBM-CD133-. We further found knockdown the expression levels of SirT1 can inhibit the drug-resistant genes, and further partially block the self-renewal and tumor restoration abilities in GBM-CD133+. The apoptotic activities of annexin V, caspase 3, and PARP were effectively induced in GBM-CD133+ treated by SirT1 siRNA and further increase radioresenitivity and temozolomide-treated effects. In addition, knock-down of SirT1 could inhibit the expression of CD133 antigen, and further decrease tumorigenic capability in orthotopic-xenotransplanted SCID mice measured by living MRI and GFP imaging. The survival studies in mice confirm that the treatment effect of chemoradiotherapy for CD133+ can be improved by the treatment of SirT1 siRNA. In sum, this result supported that SirT1 participated antiproliferation, apoptotic ability, and radiosensitizing effects in GBM-CD133+. The overexpression of Sirt1 protein in GBM-CD133+ might be a new target for GBM therapy in the future.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 183.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009