TY - JOUR T1 - Down-regulation of Deoxycytidine Kinase Enhances Acquired Resistance to Gemcitabine in Pancreatic Cancer JF - Anticancer Research JO - Anticancer Res SP - 2205 LP - 2212 VL - 28 IS - 4B AU - SEIJI OHHASHI AU - KENOKI OHUCHIDA AU - KAZUHIRO MIZUMOTO AU - HAYATO FUJITA AU - TAKUYA EGAMI AU - JUN YU AU - HIROKI TOMA AU - SHOKO SADATOMI AU - EISHI NAGAI AU - MASAO TANAKA Y1 - 2008/07/01 UR - http://ar.iiarjournals.org/content/28/4B/2205.abstract N2 - 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. Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -