Overexpression of the Orphan Receptor Nur77 and Its Translocation Induced by PCH4 May Inhibit Malignant Glioma Cell Growth and Induce Cell Apoptosis

被引：41

作者：

Chang, Li-Fu ^{[1
,2
]}

Lin, Po-Cheng ^{[1
,2
]}

Ho, Li-Ing ^{[3
]}

Liu, Po-Yen ^{[4
]}

Wu, Wan-Chen ^{[5
]}

Chiang, I-Ping ^{[6
]}

Chang, Hui-Wen ^{[6
]}

Lin, Shinn-Zong ^{[8
]}

Harn, Yeu-Chern ^{[9
]}

Harn, Horng-Jyh ^{[6
,7
]}

Chiou, Tzyy-Wen ^{[1
,2
]}

机构：

[1] Natl Dong Hwa Univ, Dept Life Sci, Shoufeng, Hualien, Taiwan

[2] Natl Dong Hwa Univ, Grad Inst Biotechnol, Shoufeng, Hualien, Taiwan

[3] Vet Gen Hosp Taipei, Dept Resp Care, Taipei, Taiwan

[4] China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan

[5] China Med Univ, Grad Inst Basic Med Sci, Taichung, Taiwan

[6] China Med Univ Hosp, Dept Pathol, Taichung 40447, Taiwan

[7] China Med Univ, Dept Med, Taichung, Taiwan

[8] China Med Univ & Hosp, Ctr Neuropsychiat, Taichung 40447, Taiwan

[9] Natl Taiwan Univ, Grad Inst Networking & Multimedia, Taipei 10764, Taiwan

来源：

JOURNAL OF SURGICAL ONCOLOGY | 2011年 / 103卷 / 05期

关键词：

glioblastoma multiform; the derivative of n-butylidenephthalide; (Z)-N-(2-(dimethylamino)ethyl)-2-(3-((3-oxoisobenzofuran-1(3H)-ylidene)methyl)phenoxy)acetamide; PCH4; apoptosis; JNK pathway; NUCLEAR RECEPTOR; BRAIN-TUMOR; GENE; EXPRESSION; ACTIVATION; KINASE; TRANSCRIPTION; LUNG; MGMT; TR3;

D O I：

10.1002/jso.21809

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：442 / 450

页数：9

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