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.
|Number of pages||8|
|Issue number||4 B|
|Publication status||Published - Jul 2008|
All Science Journal Classification (ASJC) codes
- Cancer Research