Enhanced radiosensitivity and radiation-induced apoptosis in glioma CD133-positive cells by knockdown of SirT1 expression.
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.
Chang
Charn-Jung
CJ
Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Hsu
Chuan-Chih
CC
Yung
Ming-Chi
MC
Chen
Kai-Yun
KY
Tzao
Ching
C
Wu
Wei-Fong
WF
Chou
Hsiang-Yun
HY
Lee
Yi-Yen
YY
Lu
Kai-Hsi
KH
Chiou
Shih-Hwa
SH
Ma
Hsin-I
HI
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics / Q000532:radiotherapy*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics*
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins