Down-regulation of Deoxycytidine Kinase Enhances Acquired Resistance to Gemcitabine in Pancreatic Cancer

Background: The functional roles of deoxycytidine kinase (dCK) in acquired resistance to gemcitabine remain unknown in pancreatic cancer. Here, the functional involvement of dCK in gemcitabine-resistance of pancreatic cancer was investigated. Materials and Methods: The levels of the dCK gene as well...

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Bibliographic Details
Published in:Anticancer research 2008-07, Vol.28 (4B), p.2205-2212
Main Authors: Ohhashi, Seiji, Ohuchida, Kenoki, Mizumoto, Kazuhiro, Fujita, Hayato, Egami, Takuya, Yu, Jun, Toma, Hiroki, Sadatomi, Shoko, Nagai, Eishi, Tanaka, Masao
Format: Article
Language:English
Subjects:
Antimetabolites, Antineoplastic - pharmacokinetics
Antimetabolites, Antineoplastic - pharmacology
Biological and medical sciences
Cell Line, Tumor
Deoxycytidine - analogs & derivatives
Deoxycytidine - pharmacokinetics
Deoxycytidine - pharmacology
Deoxycytidine Kinase - antagonists & inhibitors
Deoxycytidine Kinase - biosynthesis
Deoxycytidine Kinase - genetics
Down-Regulation
Drug Resistance, Neoplasm
Equilibrative Nucleoside Transporter 1 - antagonists & inhibitors
Equilibrative Nucleoside Transporter 1 - biosynthesis
Equilibrative Nucleoside Transporter 1 - genetics
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - enzymology
Pancreatic Neoplasms - genetics
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleoside Diphosphate Reductase - antagonists & inhibitors
Ribonucleoside Diphosphate Reductase - biosynthesis
Ribonucleoside Diphosphate Reductase - genetics
RNA, Small Interfering - genetics
Tumor Suppressor Proteins - antagonists & inhibitors
Tumor Suppressor Proteins - biosynthesis
Tumor Suppressor Proteins - genetics
Tumors
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Summary:Background: The functional roles of deoxycytidine kinase (dCK) in acquired resistance to gemcitabine remain unknown in pancreatic cancer. Here, the functional involvement of dCK in gemcitabine-resistance of pancreatic cancer was investigated. Materials and Methods: The levels of the dCK gene as well as other gemcitabine-related genes (hENT1, RRM1 and RRM2) were analyzed in gemcitabine-resistant pancreatic cancer cells (GR cells) using quantitative real-time reverse transcription polymerase chain reaction. The effects of inhibition of these genes on sensitivity to gemcitabine were evaluated. Results: In GR cells, expression of dCK was significantly reduced compared with that of parental cells (p
ISSN:0250-7005
1791-7530