期刊
ONCOTARGET
卷 8, 期 26, 页码 43237-43247出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18018
关键词
glioma stem cells; demethoxycurcumin; reactive oxygen species; caspase-3; ABCG2
资金
- National Natural Science Foundation of China [81370062, 81000963]
- Jiangsu Province's 333 Talent Program [BRA2011046]
- Six talents peak project in Jiangsu Province [WSN146]
- Jiangsu Province's Natural Science Foundation [BK2012670]
- Medical Research Foundation by Jiangsu Province Health Department [YG201301, Z201215, Z201318]
- Clinical Technology Development of Jiangsu University [JLY20120053]
- Brain Clinic and Basic Research Team Program of the First People's Hospital of Kunshan [KYC004]
We analyzed the role of ABCG2, a drug transporter, in determining the sensitivity of glioma stem cells (GSCs) to demethoxycurcumin (DMC). We first demonstrated that ABCG2 is more highly expressed in GSCs than primary astrocytes. Modulation of ABCG2 levels in GSCs by transfection of ABCG2 shRNA or a lentiviral vector encoding ABCG2 revealed an inverse relation between ABCG2 levels and DMC- induced GSC growth inhibition. Suppressing ABCG2 increased DMC- induced apoptosis and G0/G1 cell cycle arrest in GSCs. It also increased levels reactive oxygen species (ROS) in GSCs treated with DMC, resulting in increased cytochrome C and caspase- 3 activity. When GSCs transfected with ABCG2 shRNA or overexpressing ABCG2 were xenografted and the tumor-bearing, immunodeficient mice were treated with DMC, ABCG2 expression suppressed the tumor proliferation rate (T/C %). These findings demonstrate that ABCG2 expression is critical for DMC resistance in GSCs and is a potential therapeutic target for GBM.
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