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

Seiji Ohhashi, Kenoki Ouchida, Kazuhiro Mizumoto, Hayato Fujita, Takuya Egami, Jun Yu, Hiroki Toma, Shoko Sadatomi, Eishi Nagai, Masao Tanaka

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2205-2212
Number of pages8
JournalAnticancer research
Volume28
Issue number4 B
Publication statusPublished - Jul 1 2008

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gemcitabine
Deoxycytidine Kinase
Pancreatic Neoplasms
Down-Regulation
Cell Proliferation
Small Interfering RNA
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer. / Ohhashi, Seiji; Ouchida, Kenoki; Mizumoto, Kazuhiro; Fujita, Hayato; Egami, Takuya; Yu, Jun; Toma, Hiroki; Sadatomi, Shoko; Nagai, Eishi; Tanaka, Masao.

In: Anticancer research, Vol. 28, No. 4 B, 01.07.2008, p. 2205-2212.

Research output: Contribution to journalArticle

Ohhashi, S, Ouchida, K, Mizumoto, K, Fujita, H, Egami, T, Yu, J, Toma, H, Sadatomi, S, Nagai, E & Tanaka, M 2008, 'Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer', Anticancer research, vol. 28, no. 4 B, pp. 2205-2212.
Ohhashi, Seiji ; Ouchida, Kenoki ; Mizumoto, Kazuhiro ; Fujita, Hayato ; Egami, Takuya ; Yu, Jun ; Toma, Hiroki ; Sadatomi, Shoko ; Nagai, Eishi ; Tanaka, Masao. / Down-regulation of deoxycytidine kinase enhances acquired resistance to gemcitabine in pancreatic cancer. In: Anticancer research. 2008 ; Vol. 28, No. 4 B. pp. 2205-2212.
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AU - Egami, Takuya

AU - Yu, Jun

AU - Toma, Hiroki

AU - Sadatomi, Shoko

AU - Nagai, Eishi

AU - Tanaka, Masao

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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.

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