Document Detail

Dexamethasone reduced invasiveness of human malignant glioblastoma cells through a MAPK phosphatase-1 (MKP-1) dependent mechanism.
MedLine Citation:
PMID:  18652821     Owner:  NLM     Status:  MEDLINE    
Dexamethasone has been shown to inhibit tumor invasiveness. In the present study, the effects of dexamethasone on matrix metalloproteinases-2 (MMP-2) secretion, cell invasiveness, and intravasation in human U87MG glioma cells were examined. Dexamethasone decreased MMP-2 secretion and cell invasiveness in human glioma cells. Incubation of cells with dexamethasone increased mitogen activated protein kinase phosphatase-1 (MKP-1) expression. Ectopic expression of MKP-1 decreased cell invasiveness in vitro and intravasation in vivo. Because expression of inducible nitric oxide synthase (iNOS) has been implicated in the progression of malignant gliomas, we next investigated the possible roles of NO(-) in MMP-2 secretion and cell invasiveness in human U87MG glioma cells. Treatment of glioma cells with nitric oxide donor, sodium nitroprusside (SNP), increased MMP-2 secretion and the capacity of cell invasion in U87MG cells. Addition of dexamethasone or ectopic expression of wild-type MKP-1 suppressed the SNP-stimulated MMP-2 activation and glioma cell invasiveness in U87MG cells. Taken together, these results suggest that dexamethasone may suppress MMP-2 secretion and cell invasion through MKP-1 induction in human glioma cells.
Yu-Min Lin; Hsun-Jin Jan; Chin-Cheng Lee; Hsiao-Yi Tao; Yu-Lueng Shih; Hen-Wei Wei; Horng-Mo Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-09
Journal Detail:
Title:  European journal of pharmacology     Volume:  593     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-26     Completed Date:  2008-11-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-9     Citation Subset:  IM    
Department of Internal Medicine, National Defense Medical Center, Shin Kong Memorial Hospital, Taipei 111, Taiwan.
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MeSH Terms
Antineoplastic Agents, Hormonal / therapeutic use*
Blotting, Western
Cell Line, Tumor
Chorioallantoic Membrane / metabolism
Dexamethasone / therapeutic use*
Drug Combinations
Dual Specificity Phosphatase 1 / metabolism*
Glioblastoma / drug therapy*,  enzymology*,  pathology
Mitogen-Activated Protein Kinase 1 / metabolism
Neoplasm Invasiveness / pathology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / biosynthesis
Plasmids / genetics
Tetrazolium Salts
Reg. No./Substance:
0/Antineoplastic Agents, Hormonal; 0/Drug Combinations; 0/Laminin; 0/Proteoglycans; 0/Tetrazolium Salts; 0/Thiazoles; 10102-43-9/Nitric Oxide; 119978-18-6/matrigel; 298-93-1/thiazolyl blue; 50-02-2/Dexamethasone; 9007-34-5/Collagen; EC Oxide Synthase Type II; EC Protein Kinase 1; EC protein, human; EC Specificity Phosphatase 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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