PT  - JOURNAL ARTICLE
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
TI  - Down-regulation of Deoxycytidine Kinase Enhances Acquired Resistance to Gemcitabine in Pancreatic Cancer
DP  - 2008 Jul 01
TA  - Anticancer Research
PG  - 2205--2212
VI  - 28
IP  - 4B
4099  - http://ar.iiarjournals.org/content/28/4B/2205.short
4100  - http://ar.iiarjournals.org/content/28/4B/2205.full
SO  - Anticancer Res2008 Jul 01; 28
AB  - 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