Overexpression of the Orphan Receptor Nur77 and Its Translocation Induced by PCH4 May Inhibit Malignant Glioma Cell Growth and Induce Cell Apoptosis
Overexpression of the Orphan Receptor Nur77 and Its Translocation Induced by PCH4 May Inhibit Malignant Glioma Cell Growth and Induce Cell Apoptosis
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DOI：
10.1002/jso.21809
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发表时间：
2011-04-01
影响因子：
2.5
通讯作者：
Chiou, Tzyy-Wen
中科院分区：
文献类型：
--
作者：
Chang, Li-Fu;Lin, Po-Cheng;Chiou, Tzyy-Wen
背景：在之前的研究中，当归的天然化合物正丁苯酞（BP）具有抗多形性胶质母细胞瘤（GBM）细胞作用。在这项研究中，我们修改了 BP 结构以增强抗 GBM 细胞作用。体外和体内测试了 BP 的一种衍生物 (Z)-N-(2-(二甲基氨基)乙基)-2-(3-((3-氧代异苯并呋喃-1(3H)-亚基)甲基)苯氧基)乙酰胺 (PCH4) 的抗 GBM 细胞作用。方法：采用 MTT 法和 PI/Annexin V 法检测 评估 PCH4 的抗 GBM 作用。通过RT-PCR和Western blot检测Nur77的表达和易位。 Nur77 siRNA 用于下调 Nur77 表达。采用JNK抑制剂(SP600125)阻断JNK通路。结果：PCH4的抗GBM作用是BP的四倍。 PCH4对DBTRG-05MG细胞的IC50为50μg/ml。 Nur77 表达和从细胞核到细胞质的易位在 PCH4 诱导的细胞凋亡中很重要。此外，Nur77 siRNA 下调 PCH4 诱导的 Nur77 表达可减少 PCH4 诱导的细胞凋亡。此外，PCH4诱导的细胞凋亡与JNK通路相关。 JNK抑制剂SP600125抑制Nur77 mRNA表达，减少PCH4诱导的细胞凋亡。结论：综上所述，BP的衍生物PCH4通过JNK途径诱导Nur77介导的细胞凋亡，这种与BP不同的机制可能解释了其对GBM抗肿瘤作用增强的原因。 J.外科医生。安科尔。 2011； 103：442-450。 (C) 2011 Wiley-Liss, Inc.
Background: In previous study, n-butylidenephthalide (BP), a natural compound from Angelica sinensis, has anti-glioblastoma multiform (GBM) cell effects. In this study, we modified BP structure to increase anti-GBM cell effects. The anti-GBM cell effects of one derivative of BP, (Z)-N-(2-(dimethylamino)ethyl)-2-(3-((3-oxoisobenzofuran-1(3H)-ylidene)methyl)phenoxy)acetamide (PCH4) were tested in vitro and in vivo.Methods: MTT assay and PI/Annexin V assay were performed to evaluate the anti-GBM effects of PCH4. The Nur77 expression and translocation were assayed by RT-PCR and Western blot. The Nur77 siRNA was used to downregulate the Nur77 expression. The JNK inhibitor (SP600125) was used to block the JNK pathway.Results: The anti-GBM effect of PCH4 is four times more than BP. The IC50 of PCH4 on DBTRG-05MG cells was 50 mu g/ml. Nur77 expression and translocation from the nucleus to the cytoplasm were important in PCH4-induced apoptosis. Furthermore, the downregulation of PCH4-induced Nur77 expression by Nur77 siRNA reduced PCH4-induced apoptosis. In addition, PCH4-induced apoptosis was associated with the JNK pathway. The JNK inhibitor, SP600125, inhibited Nur77 mRNA expression and reduced PCH4-induced apoptosis.Conclusions: In conclusion, PCH4, a derivative of BP, induced Nur77-mediated apoptosis via the JNK pathway and this mechanism, which is different from that of BP, may explain the increase in the anti-tumor effects on GBM. J. Surg. Oncol. 2011; 103: 442-450. (C) 2011 Wiley-Liss, Inc.