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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Pigment epithelial-derived factor inhibits c-FLIP expression and assists ciglitazone-induced apoptosis in hepatocellular carcinoma.
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Pigment epithelial-derived factor inhibits c-FLIP expression and assists ciglitazone-induced apoptosis in hepatocellular carcinoma.

机译：色素上皮衍生因子抑制c-FLIP表达并协助西格列酮诱导的肝细胞癌细胞凋亡。

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摘要

BACKGROUND: Pigment epithelial-derived factor (PEDF) displays its antiangiogenicity by mechanisms partly involving suppression of the cellular FADD-like IL-1beta-converting enzyme (FLICE)/caspase-8-inhibitory protein (c-FLIP) expression in endothelial cells. c-Jun NH(2)-terminal kinases (JNKs) regulate c-FLIP expression in endothelial cells. The effect of PEDF on other cells remains unclear. MATERIALS AND METHODS: c-FLIP expression was assessed by semi-quantitative reverse transcriptase (RT)-PCR and immunoblotting. Pharmacological inhibitors were used to examine the involvement of PEDF signaling. RESULTS: PEDF can also down-regulate c-FLIP expression in hepatoma cell line SK-Hep-1. PEDF induced p38 kinase phosphorylation in SK-Hep-1 cells. The effect of PEDF on c-FLIP expression was attenuated by p38 kinase inhibitor, but not JNK inhibitor. In addition, PEDF pretreatment significantly increased the sensitivity of SK-Hep-1 cells to procaspase-8 cleavage and apoptosis induced by ciglitazone. CONCLUSION: PEDF-induced p38 signaling causes c-FLIP down-regulation in SK-Hep-1. We postulate PEDF has a novel effect on apoptotic inducible activity in hepatoma cells.
机译：背景：色素上皮衍生因子（PEDF）通过部分抑制内皮细胞中细胞FADD样IL-1β转换酶（FLICE）/ caspase-8抑制蛋白（c-FLIP）的表达来发挥抗血管生成作用。 c-Jun NH（2）-末端激酶（JNKs）调节内皮细胞中的c-FLIP表达。 PEDF对其他细胞的作用仍不清楚。材料与方法：通过半定量逆转录酶（RT）-PCR和免疫印迹法评估c-FLIP的表达。使用药理学抑制剂来检查PEDF信号传导的参与。结果：PEDF还可以下调肝癌细胞SK-Hep-1中的c-FLIP表达。 PEDF诱导SK-Hep-1细胞中的p38激酶磷酸化。 PEDF对c-FLIP表达的影响被p38激酶抑制剂（而非JNK抑制剂）减弱。此外，PEDF预处理显着提高了SK-Hep-1细胞对西格列酮诱导的procaspase-8裂解和凋亡的敏感性。结论：PEDF诱导的p38信号转导导致SK-Hep-1中c-FLIP的下调。我们假设PEDF对肝癌细胞中的凋亡诱导活性具有新的作用。

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