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Ref Type Journal Article
PMID (23855452)
Authors Duong HQ, Hong YB, Kim JS, Lee HS, Yi YW, Kim YJ, Wang A, Zhao W, Cho CH, Seong YS, Bae I
Title Inhibition of checkpoint kinase 2 (CHK2) enhances sensitivity of pancreatic adenocarcinoma cells to gemcitabine.
Journal Vol Issue Date Pages Journal Short Title
Journal of cellular and molecular medicine 17 10 2013 Oct 1261-70 J Cell Mol Med
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
NSC109555 NSC109555 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
NSC109555 NSC-109555|NSC 109555 CHK2 Inhibitor 7 NSC109555 is an ATP-competitive inhibitor of CHK2 with the potential to enhance antitumor effects of chemotherapeutic agents (PMID: 23855452).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References