Document Detail

Adenoviral therapy is more effective in gemcitabine-resistant pancreatic cancer than in gemcitabine-sensitive cells.
MedLine Citation:
PMID:  21508376     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Although gemcitabine is the standard treatment for pancreatic cancer, this particular type of cancer develops rapidly and has intrinsic chemoresistance. Chemoresistance plays a critical role in tumor progression, invasion and migration. Nevertheless, the effect of adenoviral therapy on chemoresistant cancer cells has not been studied. In this study, we compared the efficacy of adenoviral therapy in parental and chemoresistant pancreatic cancer cells.
MATERIALS AND METHODS: To establish gemcitabine-resistant cells, pancreatic cancer SUIT2 cells were exposed to increasing concentrations of gemcitabine. Both parental and chemoresistant cells were infected with adenoviruses expressing either green fluorescent protein (Ad-GFP) or the hepatocyte growth factor antagonist, NK4 (Ad-NK4). To investigate the transduction efficacy, GFP expression and NK4 concentrations were measured and an invasion assay was used to investigate the efficacy of the adenoviral therapy.
RESULTS: The 50% inhibitory concentration of gemcitabine was <10 nM in the parental SUIT-2 cells, while it was >1 μM in gemcitabine-resistant cells. A large number of gemcitabine-resistant cells were GFP-positive compared with only a small number of parental cells (p<0.05). The NK4 expression level was significantly higher in gemcitabine-resistant cells than in parental cells (p<0.05). The supernatant from Ad-NK4-infected gemcitabine-resistant cells significantly inhibited the invasion of cancer cells compared with that from Ad-NK4-infected parental cells (p<0.05).
CONCLUSION: Both the efficiency of transduction and the therapeutic efficacy of adenoviral therapy were higher in gemcitabine-resistant cells than in parental cells, suggesting that adenoviral gene therapy is more effective in patients with gemcitabine-resistant pancreatic cancer.
Takaharu Yasui; Kenoki Ohuchida; Ming Zhao; Lin Cui; Manabu Onimaru; Takuya Egami; Hayato Fujita; Takao Ohtsuka; Kazuhiro Mizumoto; Kunio Matsumoto; Masao Tanaka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  31     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-21     Completed Date:  2011-07-26     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1279-87     Citation Subset:  IM    
Department of Surgery and Oncology, Kyushu University, Fukuoka 812-8582, Japan.
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MeSH Terms
Adenoviridae / genetics*
Antimetabolites, Antineoplastic / therapeutic use
Blotting, Western
Cell Adhesion
Cell Line, Tumor
Cell Movement
Cell Proliferation
Deoxycytidine / analogs & derivatives*,  therapeutic use
Drug Resistance, Neoplasm / genetics*
Genetic Therapy*
Green Fluorescent Proteins / genetics
Hepatocyte Growth Factor / genetics*
Pancreatic Neoplasms / genetics*,  therapy*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Transgenes / physiology
Tumor Markers, Biological / genetics
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/HGF protein, human; 0/RNA, Messenger; 0/Tumor Markers, Biological; 0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins; 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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