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

被引:52
作者
Maehara, S
Tanaka, S
Shimada, M
Shirabe, K
Saito, Y
Takahashi, K
Maehara, Y
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Higashi Ku, Fukuoka 8128582, Japan
[2] Natl Inst Adv Ind Sci & Technol, Human Stress Signal Res Ctr, Osaka, Japan
[3] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Hyg Chem, Sapporo, Hokkaido, Japan
关键词
microarray; sensitivity; free radical scavenger; reactive oxygen species;
D O I
10.1002/ijc.20304
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 KLMI, we established a resistant cell line KLMI-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 KLMI-R cell line but not in the KLMI cell line. Administration of selenoprotein P inhibited the gemcitabine-induced cytotoxicity in the pancreatic cell lines. The levels of intracellular reactive oxygen species (ROS) were increased in the KLMI cells by gemcitabine, but selenoprotein P suppressed the gemcitabine-induced ROS levels. Furthermore interferon-gamma suppressed the expression of selenoprotein P mRNA and increased intracellular ROS level, leading to the recovery of the gemcitabine sensitivity in KLMI-R. These results suggest a novel mechanism that selenoprotein P reduces the intracellular ROS levels, resulting in the insusceptibility to gemcitabine. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:184 / 189
页数:6
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