Pirfenidone inhibits TGF-β expression in malignant glioma cells

被引:67
作者
Burghardt, Isabel
Tritschler, Felix
Opitz, Christiane A.
Frank, Brigitte
Weller, Michael
Wick, Wolfgang
机构
[1] Univ Tubingen, Mol Neurooncol Lab, Dept Gen Neurol, D-72076 Tubingen, Germany
[2] Univ Tubingen, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany
关键词
pirfenidone; TGF-beta; furin; MMP-11 (stromelysin-3); glioma;
D O I
10.1016/j.bbrc.2007.01.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Due to its immunosuppressive properties, the cytokine transforming growth factor (TGF)-beta has become a promising target in the experimental treatment of human malignant gliomas. Here, we report that the antifibrotic drug 5-methyl-1-phenyl-2-(1H)-pyridone (pirfenidone, PFD) elicits growth-inhibitory effects and reduces TGF-beta(2) protein levels in human glioma cell lines. This reduction in TGF-beta(2) is biologically relevant since PFD treatment reduces the growth inhibition of TGF-beta-sensitive CCL-64 cells mediated by conditioned media of glioma cells. The downregulation of TGF-beta is mediated at multiple levels. PFD leads to a reduction of TGF-beta(2) mRNA levels and of the mature TGF-beta(2) protein due to decreased expression and direct inhibition of the TGF-beta pro-protein convertase furin. In addition, PFD reduces the protein levels of the matrix metalloproteinase (MMP)-11, a TGF-beta target gene and furin substrate involved in carcinogenesis. These data define PFD or PFD-related agents as promising agents for human cancers associated with enhanced TGF-beta activity. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:542 / 547
页数:6
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