In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 17, No. 10 ( 2013-10), p. 1261-1270
Abstract:
Checkpoint kinase 2 ( CHK 2) plays pivotal function as an effector of cell cycle checkpoint arrest following DNA damage. Recently, we found that co‐treatment of NSC 109555 (a potent and selective CHK 2 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 Bx PC ‐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 CHK 2 by si RNA enhanced GEM ‐induced apoptotic cell death. These findings suggest that inhibition of CHK 2 would be a beneficial therapeutic approach for pancreatic cancer therapy in clinical treatment.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2013.17.issue-10
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2076114-4
detail.hit.zdb_id:
2074559-X