Document Detail


Effects of NFkappaB decoy oligonucleotides released from biodegradable polymer microparticles on a glioblastoma cell line.
MedLine Citation:
PMID:  12059028     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The objectives of this study were to investigate a nuclear factor-kappa B (NFkappaB) decoy oligonucleotide (ODN) strategy on the inhibition of glioblastoma (GBM) cell line growth and to evaluate a poly(DL-lactic-co-glycolic acid) (PLGA) microparticle delivery system for the NFKB decoy ODNs in vitro. We have demonstrated that NFkappaB activation is important in regulating GBM cell line growth. Aberrant nuclear expression of NFkappaB was found in a panel of GBM cell lines, while untransformed glial cells did not display NFkappaB activity. Nuclear translocation of NFkappaB was inhibited by using a 'decoy" ODN strategy. NFkappaB decoy ODNs designed to inhibit NFkappaB resulted in a significant reduction in cell number (up to 45%) compared to control cultures after 2 days. The reduction in cell number correlated with a decrease in cyclin D1 protein expression and a commensurate decrease in Cdk-4 activity. These results provide evidence suggesting that NFkappaB mediates cell cycle progression and demonstrates a mechanism linking increased NFkappaB activity with GBM cell growth and cell cycle disregulation. Decoy ODNs were encapsulated at a yield of 66% in PLGA microparticles and released in a controlled manner in phosphate buffered saline for up to 28 days. Approximately 83% of entrapped ODNs were released by day 28. During 3 days of GBM cell line culture, the released decoy ODNs retained their biologic activity and led to significantly reduced cell number as compared to control cultures. These findings offer a potential therapeutic strategy in the control of human GBM cell line growth in vitro and suggest that PLGA microparticles may be appropriate as delivery vehicles for the "decoy" ODN strategy.
Authors:
Jagjit S Gill; Xun Zhu; Michael J Moore; Lichun Lu; Michael J Yaszemski; Anthony J Windebank
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biomaterials     Volume:  23     ISSN:  0142-9612     ISO Abbreviation:  Biomaterials     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-06-12     Completed Date:  2002-12-06     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  2773-81     Citation Subset:  IM    
Affiliation:
Molecular Neuroscience Program, Mayo Clinic, Rochester, MN 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Biocompatible Materials / pharmacology*
Biodegradation, Environmental*
Blotting, Western
Cell Division
Cell Line
Cells, Cultured
Cyclin D1 / metabolism
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinases / metabolism
Glioblastoma / drug therapy
Humans
Immunoblotting
Kinetics
Lactic Acid / pharmacology
NF-kappa B / metabolism,  pharmacology*
Neuroglia / cytology
Oligonucleotides / pharmacology*
Polyglycolic Acid / pharmacology
Polymers / pharmacology*
Proto-Oncogene Proteins*
Time Factors
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
NS39764/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/NF-kappa B; 0/Oligonucleotides; 0/Polymers; 0/Proto-Oncogene Proteins; 0/polylactic acid-polyglycolic acid copolymer; 136601-57-5/Cyclin D1; 26009-03-0/Polyglycolic Acid; 50-21-5/Lactic Acid; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases

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


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