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The role of STAT-6 as a key transcription regulator in HeLa cell death induced by IFN-γ/TNF-α co-immobilized on nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
6186 467 2014 12 PDF Available
Title
The role of STAT-6 as a key transcription regulator in HeLa cell death induced by IFN-γ/TNF-α co-immobilized on nanoparticles
Abstract

Based on the fact that the transcription of STAT-1 plus its Serine 727 and Tyrosine 701 phosphorylation is not the pre-requisite for the cell death signal transduction in the IFN-γ signaling pathway induced by co-immobilized IFN-γ/TNF-α, we investigate both in vitro and in vivo the key transcription regulators to promote the signal transduction of HeLa cells. It is found that IFN-γ R2 is the important death signal receptor in the HeLa cell death by RNA interference. Checking the expression of the whole transcription (STAT) protein family reveals that STAT-6 is highly expressed in comparison with the other STAT proteins. The gene silence of IFN-γ R2 leads to the down-regulation of STAT-6 and phosphorylation-STAT-6 (p-STAT-6) expressions. The successful gene silence of STAT-6 results in the reduction of HeLa cell programmed death and the expression of several important key factors related to programmed cell death (p53, Bcl-2, and Bax). More importantly, our in vivo experiments by injecting nanoparticle drug carriers with the co-immobilized IFN-γ/TNF-α into nude mice model confirm the high expression of STAT-6 and p-STAT-6. It is thus concluded that, in response to IFN-γ, the co-immobilized IFN-γ/TNF-α unusually promotes the activation of STAT-6 rather than STAT-1, resulting in the enhanced cell programmed death in HeLa. The present work reveals the gene-level molecular mechanism of IFN-γ/TNF-α co-immobilized on biomaterials as a potentially effective therapy against cancer cells.

Keywords
Co-immobilized IFN-γ/TNF-α; IFN-γ signaling pathway; STAT-6; p-STAT-6; HeLa; Magnetic nanoparticle drug carriers; Nude mice
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The role of STAT-6 as a key transcription regulator in HeLa cell death induced by IFN-γ/TNF-α co-immobilized on nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 18, June 2014, Pages 5016–5027
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us