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Research ArticleExperimental Studies

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

SEIJI OHHASHI, KENOKI OHUCHIDA, KAZUHIRO MIZUMOTO, HAYATO FUJITA, TAKUYA EGAMI, JUN YU, HIROKI TOMA, SHOKO SADATOMI, EISHI NAGAI and MASAO TANAKA
Anticancer Research July 2008, 28 (4B) 2205-2212;
SEIJI OHHASHI
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KENOKI OHUCHIDA
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  • For correspondence: kenoki@med.kyushu-u.ac.jp mizumoto@med.kyushu-u.ac.jp
KAZUHIRO MIZUMOTO
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  • For correspondence: kenoki@med.kyushu-u.ac.jp mizumoto@med.kyushu-u.ac.jp
HAYATO FUJITA
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TAKUYA EGAMI
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JUN YU
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HIROKI TOMA
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SHOKO SADATOMI
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EISHI NAGAI
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MASAO TANAKA
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Abstract

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<0.05). The dCK-targeting siRNA significantly reduced gemcitabine sensitivity (p<0.01) without affecting cell proliferation. The RRM1- and RRM2-targeting siRNAs increased gemcitabine sensitivity (p<0.05) and reduced cell proliferation even without gemcitabine treatment. The hENT-targeting siRNA did not affect gemcitabine sensitivity or cell proliferation. Conclusion: Down-regulation of dCK specifically enhanced acquired resistance to gemcitabine in pancreatic cancer cells without affecting their proliferation.

  • Gemcitabine resistance
  • pancreatic cancer
  • deoxycytidine kinase

Footnotes

  • Received March 7, 2008.
  • Revision received May 23, 2008.
  • Accepted June 2, 2008.
  • Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 28 (4B)
Anticancer Research
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July-August 2008
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Down-regulation of Deoxycytidine Kinase Enhances Acquired Resistance to Gemcitabine in Pancreatic Cancer
SEIJI OHHASHI, KENOKI OHUCHIDA, KAZUHIRO MIZUMOTO, HAYATO FUJITA, TAKUYA EGAMI, JUN YU, HIROKI TOMA, SHOKO SADATOMI, EISHI NAGAI, MASAO TANAKA
Anticancer Research Jul 2008, 28 (4B) 2205-2212;

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Down-regulation of Deoxycytidine Kinase Enhances Acquired Resistance to Gemcitabine in Pancreatic Cancer
SEIJI OHHASHI, KENOKI OHUCHIDA, KAZUHIRO MIZUMOTO, HAYATO FUJITA, TAKUYA EGAMI, JUN YU, HIROKI TOMA, SHOKO SADATOMI, EISHI NAGAI, MASAO TANAKA
Anticancer Research Jul 2008, 28 (4B) 2205-2212;
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