Knockdown of Checkpoint Kinase 1 Is Associated with the Increased Radiosensitivity of Glioblastoma Stem-Like Cells
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- Wu Jun
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology
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- Lai Guozheng
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology
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- Wan Feng
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology
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- Xiao Zhengzheng
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology
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- Zeng Lingcheng
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology
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- Wang Xiongwei
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology
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- Ye Fei
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology
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- Lei Ting
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology
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抄録
Glioblastoma multiforme is an aggressive brain tumor with a poor prognosis. The glioblastoma stem-like cells (GSCs) represent a rare fraction of human glioblastoma cells with the capacity for multi-lineage differentiation, self-renewal and exact recapitulation of the original tumor. Interestingly, GSCs are more radioresistant compared with other tumor cells. In addition, the remarkable radioresistance of GSCs has been known to promote radiotherapy failure and therefore is associated with a significantly higher risk of a local tumor recurrence. Moreover, the hyperactive cell cycle checkpoint kinase (Chk) 1 and 2 play a pivotal role in the DNA damage response including radiation and chemical therapy. Based on aforementioned, we hypothesized that knockdown of Chk1 or Chk2 might confer radiosensitivity on GSCs and thereby increases the efficiency of radiotherapy. In this study, we knocked down the expression of Chk1 or Chk2 in human GSCs using lentivirus-delivered short hairpin RNA (shRNA) to examine its effect on the radiosensitivity. After radiation, the apoptosis rate and the cell cycle of GSCs were measured with Flow Cytometry. Compared with control GSCs (apoptosis, 7.82 ± 0.38%; G2/M arrest, 60.20 ± 1.28%), Chk1 knockdown in GSCs increased the apoptosis rate (37.87 ± 0.32%) and decreased the degree of the G2/M arrest (22.37 ± 2.01%). In contrast, the radiosensitivity was not enhanced by Chk2 knockdown in GSCs. These results suggest that depletion of Chk1 may improve the radio-sensitivity of GSCs via inducing cell apoptosis. In summary, the therapy targeting Chk1 gene in the GSCs may be a novel way to treat glioblastoma.
収録刊行物
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 226 (4), 267-274, 2012
東北ジャーナル刊行会
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詳細情報 詳細情報について
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- CRID
- 1390001204243182720
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- NII論文ID
- 130004459972
- 10030612854
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- NII書誌ID
- AA00863920
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- COI
- 1:CAS:528:DC%2BC38XptVaiurg%3D
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- ISSN
- 13493329
- 00408727
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- PubMed
- 22481303
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可