Document Detail


Silencing hexokinase II gene sensitizes human colon cancer cells to 5-fluorouracil.
MedLine Citation:
PMID:  19579598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Extensive trials have indicated that cancer cells with high glycolytic activity exhibit decreased sensitivity to anticancer agents. Moreover, recent research has proved that a specific inhibitor of hexokinase II, which is a key glycolytic enzyme, may enhance the activity of anticancer drugs. The purpose of this study is to further investigate the effect and mechanisms of hexokinase II on chemosensitivity of colon cancer cells to 5-fluorouracil. METHODOLOGY: The expression of hexokinase II gene was down regulated by RNA interference in colon cancer cell line LoVo, then the IC50 value of 5-fluorouracil to LoVo cells was carried out by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the protein expression of hexokinase II and thymidylate synthas by Western blot analysis Meanwhile, cell apoptosis and mitochondrial membrane potential were assessed by flow cytometry. Caspase-3 activity was also determined by its substrate color reaction. RESULTS: Down-regulation of the hexokinase II gene of LoVo cells resulted in decreased IC50 value of 5-fluorouracil and increased apoptosis rate, respectively. Furthermore, silencing hexokinase II of LoVo cells induced loss of mitochondrial membrane potential, activation of caspase-3, and inhibition of thymidylate synthase expression. CONCLUSIONS: Our findings suggest targeting hexokinase II has a potential role in the combination 5-fluorouracil treatments of colon cancer.
Authors:
Qiuping Peng; Jinming Zhou; Qi Zhou; Feng Pan; Daping Zhong; Houjie Liang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hepato-gastroenterology     Volume:  56     ISSN:  0172-6390     ISO Abbreviation:  Hepatogastroenterology     Publication Date:    2009 Mar-Apr
Date Detail:
Created Date:  2009-07-07     Completed Date:  2009-08-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8007849     Medline TA:  Hepatogastroenterology     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  355-60     Citation Subset:  IM    
Affiliation:
Department of Oncology, Southwest Hospital, The Third Military Medical University Chongqing 400038, PR China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  genetics
Blotting, Western
Caspase 3 / metabolism
Cell Line, Tumor
Colonic Neoplasms / drug therapy,  enzymology*,  pathology*
Down-Regulation / drug effects
Enzyme Activation / drug effects
Fluorouracil / pharmacology*
Gene Expression Regulation, Neoplastic
Gene Silencing / drug effects*
Hexokinase / genetics*,  metabolism
Humans
Membrane Potential, Mitochondrial / drug effects,  genetics
RNA Interference / drug effects
Thymidylate Synthase / metabolism
Transfection
Chemical
Reg. No./Substance:
51-21-8/Fluorouracil; EC 2.1.1.45/Thymidylate Synthase; EC 2.7.1.1/Hexokinase; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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