Selenoprotein P, as a predictor for evaluating gemcitabine resistance in human pancreatic cancer cells

Shin Ichiro Maehara, Shinji Tanaka, Mitsuo Shimada, Ken Shirabe, Yoshiro Saito, Kazuhiko Takahashi, Yoshihiko Maehara

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Abstract

Gemcitabine is a new standard chemotherapeutic agent used in the treatment of pancreatic cancer, but the mechanisms of gemcitabine sensitivity are still controversial. In our study to determine a mechanism that regulates gemcitabine sensitivity, we carried out molecular analysis on the susceptibility of the pancreatic cancer cells. Using a gemcitabine-sensitive pancreatic cancer cell line KLM1, we established a resistant cell line KLM1-R exhibiting a 20-fold IC50-value (the concentration of gemcitabine causing 50% growth inhibition). Microarray analysis of genes showed specific expression of selenoprotein P, one of the anti-oxidants, in the KLM1-R cell line but not in the KLM1 cell line. Administration of seleno-protein P inhibited the gemcitabine-induced cytotoxicity in the pancreatic cell lines. The levels of intracellular reactive oxygen species (ROS) were increased in the KLM1 cells by gemcitabine, but selenoprotein P suppressed the gemcitabine-induced ROS levels. Furthermore interferon-γ suppressed the expression of selenoprotein P mRNA and increased intracellular ROS level, leading to the recovery of the gemcitabine sensitivity in KLM1-R. These results suggest a novel mechanism that selenoprotein P reduces the intracellular ROS levels, resulting in the insusceptibility to gemcitabine.

Original languageEnglish
Pages (from-to)184-189
Number of pages6
JournalInternational Journal of Cancer
Volume112
Issue number2
DOIs
Publication statusPublished - Nov 1 2004

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Maehara, S. I., Tanaka, S., Shimada, M., Shirabe, K., Saito, Y., Takahashi, K., & Maehara, Y. (2004). Selenoprotein P, as a predictor for evaluating gemcitabine resistance in human pancreatic cancer cells. International Journal of Cancer, 112(2), 184-189. https://doi.org/10.1002/ijc.20304