Reduction of the antiapoptotic protein cFLIP enhances the susceptibility of human renal cancer cells to TRAIL apoptosis
Reduction of the antiapoptotic protein cFLIP enhances the susceptibility of human renal cancer cells to TRAIL apoptosis
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DOI：
10.1007/s00262-004-0595-8
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发表时间：
2005-05-01
影响因子：
5.8
通讯作者：
Sayers, TJ
中科院分区：
文献类型：
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作者：
Brooks, AD;Sayers, TJ
通过环己亚胺（CHX）处理，人肾癌细胞（RCCs）对肿瘤坏死因子（TNF）相关的凋亡诱导配体（TRAIL）的凋亡作用敏感。与先前的研究相反，在所有研究的rcc中，环己亚胺治疗后观察到细胞FLICE （fas相关的死亡结构域样il -1 β转换酶）抑制蛋白（cFLIP）水平迅速而急剧下降。这种cFLIP减少的明确检测依赖于用于检测cFLIP的特定抗体制备的质量。环己亚胺处理未引起前caspase-8水平或TRAIL受体细胞表面表达的重大变化。因此，环己亚胺处理导致caspase-8与cFLIP比值增加，这与trail介导的细胞凋亡致敏相关。此外，用cFLIP小干扰寡核糖核苷酸（siRNA）处理人rcc可导致cFLIP蛋白减少，并使细胞对trail介导的凋亡敏感。我们得出结论，在TRAIL信号通路完整的情况下，仅cFLIP的显著减少就足以使人rcc对TRAIL细胞凋亡敏感。
Human renal carcinoma cells (RCCs) were sensitized to the apoptotic effects of tumor necrosis factor (TNF) - related apoptosis- inducing ligand ( TRAIL), by treatment with cycloheximide (CHX). In contrast to a previous study, a rapid and dramatic decrease in levels of cellular FLICE ( Fas-associated death domain - like IL-1beta-converting enzyme) inhibitory protein (cFLIP) following cycloheximide treatment was observed in all RCCs studied. The unambiguous detection of this decrease in cFLIP was dependent on the quality of the particular antibody preparation used to detect cFLIP. Cycloheximide treatment caused no major change in levels of pro-caspase-8 or cell surface expression of TRAIL receptors. Therefore, cycloheximide treatment resulted in an increase in the pro-caspase-8 to cFLIP ratio, which correlated with sensitization to TRAIL-mediated apoptosis. Furthermore, treatment of human RCCs with small interfering oligoribonucleotides ( siRNA) for cFLIP caused a reduction of cFLIP protein and sensitized cells to TRAIL-mediated apoptosis. We concluded that in the presence of an intact TRAIL signaling pathway, a significant reduction of cFLIP alone is sufficient to sensitize human RCCs to TRAIL apoptosis.