Overexpression of FOXM1 is associated with metastases of nasopharyngeal carcinoma.

Overexpression of FOXM1 is associated with metastases of nasopharyngeal carcinoma.
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FOXM1过表达与鼻咽癌转移相关

DOI:
10.3109/03009734.2014.960053
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发表时间:
2014-11
影响因子:
3.4
通讯作者:
Chen H
Chen H
中科院分区:
医学4区
文献类型:
--
作者:
Jiang L;Wang P;Chen H

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叉头盒M1(FOXM1)转录因子在许多肿瘤的转移中起重要作用。通过抑制FoxM1基因的表达,可以抑制某些肿瘤的转移潜能,但关于FoxM1和Thiostrepton在鼻咽癌转移中的功能意义及其机制的研究较少。应用免疫组织化学染色、定量逆转录聚合酶链式反应(qRT-PCR)和免疫印迹法检测FOXM1在鼻咽癌组织、正常鼻咽组织、鼻咽癌细胞系(C666-1)和鼻咽上皮细胞系(NP69)中的表达。分析FOXM1的表达与患者临床特征的相关性。此外,还检测了硫链菌素对C666-1和NP69细胞FOXM1表达的影响,以及对C666-1细胞侵袭和迁移能力的影响。用硫代链球菌素处理后,检测基质金属蛋白酶-2、基质金属蛋白酶-9、法辛-1、埃兹林和帕西林的表达。FOXM1在鼻咽癌和C666-1细胞中的表达高于正常鼻咽组织和NP69细胞。FOXM1的过表达与淋巴结转移和肿瘤分期有关。此外,硫链菌素以剂量依赖的方式抑制C666-1细胞FOXM1的表达,但对NP69细胞的影响很小。硫链菌素通过下调C666-1细胞中MMP2、MMP9、Fasin-1和Paxlin的表达,抑制C666-1细胞的迁移和侵袭能力。FOXM1的过表达与鼻咽癌的转移有关。硫链菌素通过下调FOXM1、MMP2、MMP9、Fasin-1和Paxlin的表达来抑制鼻咽癌细胞的转移能力。
The forkhead box M1 (FOXM1) transcription factor plays an important role in the metastases of many cancers. Down-regulation of FOXM1 by its inhibitor, thiostrepton, can inhibit the metastatic potential of some cancers; however, there are few studies regarding the functional significance of FOXM1 and thiostrepton in the metastases of nasopharyngeal carcinoma (NPC) and the underlying mechanism. Expression of FOXM1 in NPC, normal nasopharyngeal tissues, a NPC cell line (C666-1), and a nasopharyngeal epithelial cell line (NP69) was investigated by immunohistochemical staining, qRT-PCR, and Western blot. The correlation between FOXM1 expression and the clinical characteristics of patients was analyzed. Moreover, the effects of thiostrepton on expression of FOXM1 in C666-1 and NP69 cells, and the invasion and migration ability of C666-1 cells were examined. The expressions of MMP-2, MMP-9, fascin-1, ezrin, and paxillin were determined after treatment with thiostrepton. FOXM1 was overexpressed in NPC and C666-1 cells compared with normal nasopharyngeal tissues and NP69 cells. Overexpression of FOXM1 was associated with lymph node metastasis and advanced tumor stage. Moreover, thiostrepton inhibited expression of FOXM1 in C666-1 cells in a dose-dependent manner, but had a minimal effect on NP69 cells. Thiostrepton inhibited the migration and invasion ability of C666-1 cells by down-regulating the expression of MMP-2, MMP-9, fascin-1, and paxillin. Overexpression of FOXM1 is associated with metastases of NPC patients. Thiostrepton inhibits the metastatic ability of NPC cells by down-regulating the expression of FOXM1, MMP-2, MMP-9, fascin-1, and paxillin.
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