Pirfenidone inhibits TGF-β expression in malignant glioma cells
作者： Isabel Burghardt , Felix Tritschler , Christiane A. Opitz , Brigitte Frank , Michael Weller
DOI: 10.1016/J.BBRC.2007.01.012
关键词: Downregulation and upregulation 、 Furin 、 TGF beta receptor 2 、 Cancer research 、 Endoglin 、 Molecular biology 、 Chemistry 、 Growth inhibition 、 Transforming growth factor 、 Glioma 、 TGF alpha
摘要: Due to its immunosuppressive properties, the cytokine transforming growth factor (TGF)-beta has become a promising target in experimental treatment of human malignant gliomas. Here, we report that antifibrotic drug 5-methyl-1-phenyl-2-(1H)-pyridone (pirfenidone, PFD) elicits growth-inhibitory effects and reduces TGF-beta2 protein levels glioma cell lines. This reduction is biologically relevant since PFD inhibition TGF-beta-sensitive CCL-64 cells mediated by conditioned media cells. The downregulation TGF-beta at multiple levels. leads mRNA mature due decreased expression direct pro-protein convertase furin. In addition, matrix metalloproteinase (MMP)-11, gene furin substrate involved carcinogenesis. These data define or PFD-related agents as for cancers associated with enhanced activity.
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sci-hub.se 参考文章(27)
Wolfgang Wick, Michael Platten, Michael Weller, Glioma Cell Invasion: Regulation of Metalloproteinase Activity by TGF-β Journal of Neuro-oncology. ,vol. 53, pp. 177- 185 ,(2001) , 10.1023/A:1012209518843
D A Bravo, J B Gleason, R I Sanchez, R A Roth, R S Fuller, Accurate and efficient cleavage of the human insulin proreceptor by the human proprotein-processing protease furin. Characterization and kinetic parameters using the purified, secreted soluble protease expressed by a recombinant baculovirus. Journal of Biological Chemistry. ,vol. 269, pp. 25830- 25837 ,(1994) , 10.1016/S0021-9258(18)47322-X
D Pei, G Majmudar, S J Weiss, Hydrolytic inactivation of a breast carcinoma cell-derived serpin by human stromelysin-3. Journal of Biological Chemistry. ,vol. 269, pp. 25849- 25855 ,(1994) , 10.1016/S0021-9258(18)47324-3
Jens Leitlein, Steffen Aulwurm, Robert Waltereit, Ulrike Naumann, Bettina Wagenknecht, Wolfgang Garten, Michael Weller, Michael Platten, Processing of Immunosuppressive Pro-TGF-β1,2 by Human Glioblastoma Cells Involves Cytoplasmic and Secreted Furin-Like Proteases The Journal of Immunology. ,vol. 166, pp. 7238- 7243 ,(2001) , 10.4049/JIMMUNOL.166.12.7238
Heinz Wiendl, Meike Mitsdoerffer, Valeska Hofmeister, Jörg Wischhusen, Antje Bornemann, Richard Meyermann, Elisabeth H. Weiss, Arthur Melms, Michael Weller, A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. Journal of Immunology. ,vol. 168, pp. 4772- 4780 ,(2002) , 10.4049/JIMMUNOL.168.9.4772
Swarnalatha N. Iyer, Dallas M. Hyde, Shri N. Giri, Anti-inflammatory effect of pirfenidone in the bleomycin-hamster model of lung inflammation. Inflammation. ,vol. 24, pp. 477- 491 ,(2000) , 10.1023/A:1007068313370
Kazuhisa NAKAYAMA, Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins Biochemical Journal. ,vol. 327, pp. 625- 635 ,(1997) , 10.1042/BJ3270625
Séverine Beck, J. Ann Le Good, Marcela Guzman, Nadav Ben Haim, Karine Roy, Friedrich Beermann, Daniel B. Constam, Extraembryonic proteases regulate Nodal signalling during gastrulation. Nature Cell Biology. ,vol. 4, pp. 981- 985 ,(2002) , 10.1038/NCB890
Duanqing Pei, Stephen J. Weiss, Furin-dependent intracellular activation of the human stromelysin-3 zymogen Nature. ,vol. 375, pp. 244- 247 ,(1995) , 10.1038/375244A0
M WELLER, A FONTANA, The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-beta, T-cell apoptosis, and the immune privilege of the brain. Brain Research Reviews. ,vol. 21, pp. 128- 151 ,(1995) , 10.1016/0165-0173(95)00010-0