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Inhibition of checkpoint kinase 2 (CHK2) enhances sensitivity of pancreatic adenocarcinoma cells to gemcitabine

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Author(s)
Hong-Quan DuongYoung Bin HongJung Soon KimHee-Seok LeeYong Weon YiYeon Jeong KimAntai WangWenjing ZhaoChi Heum ChoYeon-Sun SeongInsoo Bae
Keimyung Author(s)
Cho, Chi Heum
Department
Dept. of Obstetrics & Gynecology (산부인과학)
Journal Title
Journal of Cellular and Molecular Medicine
Issued Date
2013
Volume
17
Issue
10
Keyword
Checkpoint kinase 2 (CHK2) inhibitorNSC109555gemcitabinecombinationsynergismpancreatic adenocarcinoma
Abstract
Checkpoint kinase 2 (CHK2) plays pivotal function as an effector of cell cycle checkpoint arrest following DNA damage. Recently, we found that
co-treatment of NSC109555 (a potent and selective CHK2 inhibitor) potentiated the cytotoxic effect of gemcitabine (GEM) in pancreatic cancer
MIA PaCa-2 cells. Here, we further examined whether NSC109555 could enhance the antitumour effect of GEM in pancreatic adenocarcinoma
cell lines. In this study, the combination treatment of NSC109555 plus GEM demonstrated strong synergistic antitumour effect in four pancreatic
cancer cells (MIA PaCa-2, CFPAC-1, Panc-1 and BxPC-3). In addition, the GEM/NSC109555 combination significantly increased the level of
intracellular reactive oxygen species (ROS), accompanied by induction of apoptotic cell death. Inhibition of ROS generation by N-acetyl cysteine
(NAC) significantly reversed the effect of GEM/NSC109555 in apoptosis and cytotoxicity. Furthermore, genetic knockdown of CHK2 by siRNA
enhanced GEM-induced apoptotic cell death. These findings suggest that inhibition of CHK2 would be a beneficial therapeutic approach for
pancreatic cancer therapy in clinical treatment.
Keimyung Author(s)(Kor)
조치흠
Publisher
School of Medicine
Citation
Hong-Quan Duong et al. (2013). Inhibition of checkpoint kinase 2 (CHK2) enhances sensitivity of pancreatic adenocarcinoma cells to gemcitabine. Journal of Cellular and Molecular Medicine, 17(10), 1261–1270. doi: 10.1111/jcmm.12101
Type
Article
ISSN
1582-1838
DOI
10.1111/jcmm.12101
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33967
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
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