Document Detail


Gemcitabine synergistically enhances the effect of adenovirus gene therapy through activation of the CMV promoter in pancreatic cancer cells.
MedLine Citation:
PMID:  20395979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adenovirus-mediated gene therapy shows remarkable promise as a new strategy for advanced pancreatic cancer, but satisfactory clinical results have not yet been obtained. To improve this gene therapy, we investigated the effects of gemcitabine (GEM) on transgene expression by adenoviral vectors and their biological effects. We used Ad-lacZ and adenoviral vector-expressing NK4 (Ad-NK4) as representative adenoviral vectors. These vectors express beta-galactosidase (beta-gal) and NK4 (which inhibits the invasion of cancer cells), respectively, under the control of the CMV promoter. Cells were infected with the individual adenoviruses and then treated with GEM. GEM increased beta-gal mRNA expression and beta-gal activity, and increased NK4 expression in both culture media and within infected cells, in dose-dependent manners. The increased expression of NK4 delivered by Ad-NK4 had biological effects by inhibiting the invasion of cancer cells. GEM also enhanced NK4 expression in SUIT-2 cells transfected with an NK4-expressing plasmid, suggesting that GEM enhanced CMV promoter activity. In in vivo experiments, NK4 expression within subcutaneously implanted tumors was increased in GEM-treated mice compared with control mice. These results suggest that adenovirus-mediated gene therapy with GEM may be a promising approach for treating pancreatic cancer, and that this combination therapy may decrease the risks of side effects.
Authors:
M Onimaru; K Ohuchida; T Egami; K Mizumoto; E Nagai; L Cui; H Toma; K Matsumoto; M Hashizume; M Tanaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-16
Journal Detail:
Title:  Cancer gene therapy     Volume:  17     ISSN:  1476-5500     ISO Abbreviation:  Cancer Gene Ther.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-10-22     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9432230     Medline TA:  Cancer Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  541-9     Citation Subset:  IM    
Affiliation:
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Animals
Antimetabolites, Antineoplastic / pharmacology*
Cell Line, Tumor
Combined Modality Therapy
Cytomegalovirus / genetics
Deoxycytidine / analogs & derivatives*,  pharmacology
Drug Synergism
Female
Gene Expression Regulation, Neoplastic / drug effects
Genetic Therapy / methods*
Genetic Vectors / genetics
Hepatocyte Growth Factor / biosynthesis,  genetics*
Humans
Mice
Mice, Nude
Pancreatic Neoplasms / drug therapy,  genetics,  pathology,  therapy*
Promoter Regions, Genetic
Transgenes
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/HGF protein, human; 67256-21-7/Hepatocyte Growth Factor; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine

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


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