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.
authors.affiliation: School of Life Science and Laboratory of Quantum Engineering and Quantum Materials, South China Normal University, Guangzhou 510631, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Life Science and Laboratory of Quantum Engineering and Quantum Materials, South China Normal University, Guangzhou 510631, China. Electronic address: guanyq@scnu.edu.cn.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Guan
authors.affiliation: Institute for Advanced Materials and Laboratory of Quantum Engineering and Quantum Materials, South China Normal University, Guangzhou 510631, China; Laboratory of Solid State Microstructures, Nanjing University, Nanjing 210093, China. Electronic address: liujm@nju.edu.cn.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Liu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D016923:Cell Death; D015536:Down-Regulation; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry*; D007371:Interferon-gamma / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D055767:Immobilized Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Co-immobilized IFN-γ/TNF-α; HeLa; IFN-γ signaling pathway; Magnetic nanoparticle drug carriers; Nude mice; STAT-6; p-STAT-6