Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

被引：32

作者：

Yang, Heekyoung ^{[1
,2
,3
]}

Yoon, Su Jin ^{[2
]}

Jin, Juyoun ^{[1
,2
,3
]}

Choi, Seung Ho ^{[2
]}

Seol, Ho Jun ^{[1
]}

Lee, Jung-Il ^{[1
]}

Nam, Do-Hyun ^{[1
,2
,3
,4
]}

Yoo, Hae Yong ^{[2
,4
]}

机构：

[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurosurg, Seoul 135710, South Korea

[2] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Samsung Biomed Res Inst, Seoul 135710, South Korea

[3] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Canc Stem Cell Res Ctr, Seoul 135710, South Korea

[4] Sungkyunkwan Univ, Dept Hlth Sci & Technol, Samsung Adv Inst Hlth Sci & Technol, Seoul 135710, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2011年 / 406卷 / 01期

关键词：

Chk1; inhibitor; AZD7762; Radiosensitivity; DNA damage checkpoint; CELL-CYCLE CHECKPOINTS; DOUBLE-STRAND BREAKS; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; DNA-REPAIR; ATM; ACTIVATION; CHK1; TOPBP1; ABROGATION;

D O I：

10.1016/j.bbrc.2011.01.106

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis. AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：53 / 58

页数：6

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