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CXCR4 沉默对人胶质瘤 U87 细胞系转移抑制的作用及其机制。

The effect and mechanism of CXCR4 silencing on metastasis suppression of human glioma U87 cell line.

机构信息

Department of Clinical Laboratory, Tianjin Huan Hu Hospital, Tianjin, 300060, China; Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, 300060, China.

出版信息

Anat Rec (Hoboken). 2013 Dec;296(12):1857-64. doi: 10.1002/ar.22825. Epub 2013 Oct 28.

Abstract

Tumor metastasis is the major cause of treatment failure and poor prognosis of glioma. Inhibiting metastasis has become an important therapeutic strategy for glioma treatment. CXCR4 has been proved to play an important role in the occurrence and development of tumors. In order to illustrate the effect of CXCR4 on glioma metastasis, we investigated the role of CXCR4 in U87 cells metastasis based on the CXCR4 silencing tumor cells. In this study, we found that CXCR4 silencing could suppress U87 cells invasion and adhesion potential, production of TGF-β1, IL-6, and IL-8, and blocked the G0/G1 phase of the cell cycle. We also found that CXCR4 silencing could up-regulate the mRNA and protein expression of p53, p21, and E-cadherin, and down-regulate the mRNA and protein expression of CD44 and MMP-2/-9. Meanwhile, CXCR4 silencing could decrease the phosphorylation of p-AKT and transcription activity of NF-κB promoter, and increased the phosphorylation of PTEN. The results provided a new research basis for the further study of CXCR4 gene, the screening of human glioma, as well as the target treatment for glioma and its prognosis.

摘要

肿瘤转移是导致胶质瘤治疗失败和预后不良的主要原因。抑制转移已成为胶质瘤治疗的重要治疗策略。CXCR4 已被证明在肿瘤的发生和发展中起重要作用。为了说明 CXCR4 对胶质瘤转移的影响,我们基于 CXCR4 沉默肿瘤细胞研究了 CXCR4 在 U87 细胞转移中的作用。在这项研究中,我们发现 CXCR4 沉默可抑制 U87 细胞的侵袭和黏附能力、TGF-β1、IL-6 和 IL-8 的产生,并阻断细胞周期的 G0/G1 期。我们还发现,CXCR4 沉默可上调 p53、p21 和 E-cadherin 的 mRNA 和蛋白表达,并下调 CD44 和 MMP-2/-9 的 mRNA 和蛋白表达。同时,CXCR4 沉默可降低 p-AKT 的磷酸化和 NF-κB 启动子的转录活性,并增加 PTEN 的磷酸化。这些结果为进一步研究 CXCR4 基因、筛选人类脑胶质瘤以及针对脑胶质瘤及其预后的靶向治疗提供了新的研究基础。

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