Death signal transduction induced by co-immobilized TNF-α plus IFN-γ and the development of polymeric anti-cancer drugs
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- 作者：Yan-Qing Guan ; Zhibin Li ; Jun-Ming Liu
- 关键词：HeLa ; Co-immobilized TNF-α ; plus IFN-γ ; TNFR1 ; IFNR2 ; STAT1 ; Tyrosine 701 phosphorylation
- 刊名：Biomaterials
- 出版年：2010
- 出版时间：December 2010
- 年：2010
- 卷：31
- 期：34
- 页码：9074-9085
- 全文大小：2275 K
文摘
Based on our earlier work on the apoptosis in HeLa cells induced by TNF-α plus IFN-γ, we investigate how the co-immobilized TNF-α plus IFN-γ promotes the signal transduction of HeLa cells. It is found that the free TNF-α plus IFN-γ has much stronger capability than the co-immobilized TNF-α plus IFN-γ in binding with apoptosis signaling receptors TNFR1, which allows an argument that the co-immobilized TNF-α plus IFN-γ can modulate the death pathway of HeLa cells. Subsequently, we determine the cell membrane surface receptor with which the co-immobilized TNF-α plus IFN-γ binds, and probe the expression of death receptor which induces the apoptosis pathway upstream protein FADD and TRADD. Our results reveal that the death signal transduction, induced by the co-immobilized TNF-α plus IFN-γ, is mainly realized via the IFN-γ signaling pathway rather than the TNF-α one. In addition, the transcription of STAT1 plus its Serine 727 and Tyrosine 701 phosphorylation is not the pre-requisite for inducing the cell death signal transduction. It is thus suggested that the co-immobilized TNF-α plus IFN-γ promotes the activation of some unknown key markers in response to IFN-γ, and the binding of the co-immobilized TNF-α plus IFN-γ with some other TNF-α receptors results in enhanced programmed cell death in HeLa cells.