期刊
BIOMATERIALS
卷 35, 期 18, 页码 5016-5027出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.03.004
关键词
Co-immobilized IFN-gamma/TNF-alpha; IFN-gamma signaling pathway; STAT-6; p-STAT-6; Hela; Magnetic nanoparticle drug carriers; Nude mice
资金
- National Natural Science Foundation of China [31170919, 31370967]
- Natural Science Foundation of Guangdong Province [S2011020003276, 9151063101000015]
- Scientific Research Foundation of Graduate School of South China Normal University, China [2012kyjj121]
- PCSIRT, China [IRT1243]
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-gamma signaling pathway induced by co-immobilized IFN-gamma/TNF-alpha, 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-gamma 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-gamma 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, Bc1-2, and Bax). More importantly, our in vivo experiments by injecting nanoparticle drug carriers with the co-immobilized IFN-gamma/TNF-alpha into nude mice model confirm the high expression of STAT-6 and p-STAT-6. It is thus concluded that, in response to IFN-gamma, the co-immobilized IFN-gamma/TNF-alpha 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-gamma/TNF-alpha co-immobilized on biomaterials as a potentially effective therapy against cancer cells. (C) 2014 Elsevier Ltd. All rights reserved.
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