Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer
Ohhashi, S.; Ohuchida, K.; Mizumoto, K.; Fujita, H.; Egami, T.; Yu, J.; Toma, H.; Sadatomi, S.; Nagai, E.; Tanaka, M.
Anticancer Research 28(4b): 2205-2212
2008
ISSN/ISBN: 0250-7005 PMID: 18751396 Document Number: 620875
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. 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. 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. Down-regulation of dCK specifically enhanced acquired resistance to gemcitabine in pancreatic cancer cells without affecting their proliferation.