Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer.
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.


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.


CONCLUSIONS
Down-regulation of dCK specifically enhanced acquired resistance to gemcitabine in pancreatic cancer cells without affecting their proliferation.
Ohhashi
Seiji
S
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ohuchida
Kenoki
K
Mizumoto
Kazuhiro
K
Fujita
Hayato
H
Egami
Takuya
T
Yu
Jun
J
Toma
Hiroki
H
Sadatomi
Shoko
S
Nagai
Eishi
E
Tanaka
Masao
M