Ceramide Metabolism Determines Glioma Cell Resistance to Chemotherapy

被引：24

作者：

Dumitru, Claudia Alexandra ^{[1
]}

Weller, Michael ^{[2
]}

Gulbins, Erich ^{[1
]}

机构：

[1] Univ Duisburg Essen, Dept Mol Biol, D-45122 Essen, Germany

[2] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2009年 / 221卷 / 03期

关键词：

PROSTATE-CANCER PROGRESSION; ACID SPHINGOMYELINASE; MULTIDRUG-RESISTANCE; GROWTH-FACTOR; MOLECULAR-MECHANISMS; INDUCED APOPTOSIS; PROTEIN BCRP; OVEREXPRESSION; EXPRESSION; PATHWAYS;

D O I：

10.1002/jcp.21907

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Tumor cell resistance to chemotherapy constitutes a major problem in the treatment of malignant tumors. We here investigated the role of ceramide metabolism for the resistance of glioma cells to treatment with the chemotherapeutic drug, gemcitabine. Gemcitabine triggers a marked release of ceramide in drug-sensitive cells, while glioma cells that are resistant to gemcitabine, fail to accumulate ceramide. While the release of ceramide is very similar in gemcitabine-sensitive and resistant glioma cells upon stimulation, resistant glioma cells rapidly consume ceramide upon gemcitabine treatment or exogenous sphingomyelinase stimulation. Pharmacologic or genetic inhibition of glucosyltransferases prevents ceramide consumption in resistant cells and restores sensitivity of resistant glioma cells to gemcitabine. These data suggest that glioma cell resistance to at least some chemotherapeutic drugs is mediated by rapid consumption of ceramide to prevent cell death. J. Cell. Physiol. 221: 688-695, 2009. (C) 2009 Wiley-Liss, Inc.

引用

页码：688 / 695

页数：8

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