Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell lines by involving ERK1/2 and transcriptional inhibition of MMP-2
Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell lines by involving ERK1/2 and transcriptional inhibition of MMP-2
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DOI：
10.1517/14728222.2014.992875
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发表时间：
2015-03-01
影响因子：
5.8
通讯作者：
Chen, Mu-Kuan
中科院分区：
文献类型：
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作者：
Chien, Su-Yu;Hsieh, Ming-Ju;Chen, Mu-Kuan
目的：鼻咽癌以颈淋巴转移发生率高、预后差而著称。诺比莱汀是一种柑橘多甲氧基黄酮类化合物，可以抑制肿瘤的生长和转移，在以前的研究中，这两种作用都依赖于血管生成。研究设计与方法：本研究旨在研究诺必莱汀对鼻咽癌细胞迁移和侵袭能力的影响。结果：诺比莱汀显著抑制人鼻咽癌细胞株HONE-1和NPC-BM的侵袭和迁移能力。明胶酶谱和免疫印迹结果显示，诺比莱汀抑制了基质金属蛋白酶-2的活性和蛋白水平。实时定量聚合酶链式反应和启动子检测评价了诺必莱汀对人鼻咽癌细胞基质金属蛋白酶-2表达的抑制作用。诺比莱汀可抑制基质金属蛋白酶-2的表达，上调金属蛋白酶组织抑制因子-2，下调核因子-kappaB和激活蛋白1(AP-1)信号通路的转录因子。结论：诺必莱汀可能是一种潜在的鼻咽癌转移的化学预防药物。
Objective: Nasopharyngeal carcinoma (NPC) is known for its high incidence of neck lymph node metastasis, which represents poor prognosis. Nobiletin is a citrus polymethoxyflavonoid that suppresses tumor growth and metastasis, both of which depend on angiogenesis in previous studies. However, the effect of Nobiletin on human NPC cells metastasis has not been clearly clarified.Research design and methods: In this study, we determine the effects of Nobiletin on the migration and invasion in NPC cells.Results: Nobiletin significantly inhibited migration/invasion capacities of HONE-1 and NPC-BM cell lines. The results of gelatin zymography and western blotting revealed that the activities and protein levels of the MMP-2 were inhibited by Nobiletin. Nobiletin also showed that inhibits phosphorylation of ERK1/2. Tests of the real-time PCR and promoter assays evaluated the inhibitory effects of Nobiletin on MMP-2 expression in human NPC cells. Nobiletin inhibits MMP-2 expression, up-regulating tissue inhibitor of metalloproteinase-2 and down-regulation of the transcription factors of NF-kappa B and activator protein 1 (AP-1) signaling pathways. Finally, an administration of Nobiletin effectively suppressed the tumor formation and metastasis in the NPC xenograft model in vivo.Conclusions: Nobiletin may have potential use as a chemo-preventive agent against nasopharyngeal cancer metastasis.