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CGK733 enhances multinucleated cell formation and cytotoxicity induced by taxol in Chk1-deficient HBV-positive hepatocellular carcinoma cells.
MedLine Citation:
PMID:  22564734     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hepatocellular carcinoma (HCC) is one of the most deadly human cancers. Chronic hepatitis B virus (HBV) infection is one of the predominant risk factors associated with the development of HCC and complicates the treatment of HCC. In this study, we demonstrate that a HBV-positive HCC cell line HepG2.2.15, was more resistant to chemotherapy agents than its parental HBV-negative cell line HepG2. HBV-positive HCC cells exhibited defective Chk1 phosphorylation and increased chromosomal instability. CGK733, a small molecule inhibitor reportedly targeting the kinase activities of ATM and ATR, significantly enhanced taxol-induced cytotoxicity in HBV-positive HepG2.2.15 cells. The mechanism lies in CGK733 triggers the formation of multinucleated cells thus promotes the premature mitotic exit of taxol-induced mitotic-damaged cells through multinucleation and mitotic catastrophe in HBV-positive HepG2.2.15 cells. These results suggest that CGK733 could potentially reverse the taxol resistance in HBV-positive HCC cells and may suggest a novel strategy to treat HBV-infected HCC patients.
Authors:
Huan Wang; Bin Zuo; Haibin Wang; Laifeng Ren; Peng Yang; Ming Zeng; Dan Duan; Cong Liu; Mingyuan Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-30
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  -     ISSN:  1090-2104     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-5-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China; Laboratory of Genomic-Stability, Development and Stem Cell Institute, The West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
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