Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-κB-dependent pathway that reduces uPA and MMP-9 expression

doi:10.1007/s00726-014-1838-4

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學系 > 期刊論文 > Item 310902500/17971

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: https://ir.csmu.edu.tw:8080/ir/handle/310902500/17971

题名:	Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-κB-dependent pathway that reduces uPA and MMP-9 expression
作者:	Hsieh, Shu-Ching Tsai, Jen-Pi Yang, Shun-Fa Tang, Meng-Ju Hsieh, Yi-Hsien
贡献者:	中山醫大
关键词:	Hepatocellular carcinoma cells;Metformin;Invasion;Migration;MMP-9;uPA;Sorafenib
日期:	2014
上传时间:	2017-07-13T08:44:12Z (UTC)
ISSN:	0939-4451
摘要:	Abstract Metformin has been shown to exert anti-cancer activities in several cancer cells and animal models. However, the molecular mechanisms of its anti-metastatic activities remain poorly understood and warrant further investigation. The aims of this study were to evaluate the ability of metformin to inhibit the migration and invasion of hepatocellular carcinoma (HCC) cells and identify its effects on signaling pathways. Our data indicate that metformin inhibits the migration and invasion of human HCC cells. Metformin was also found to significantly inhibit the expression and secretion of MMP-9 and uPA in HCC cells, and suppress the phosphorylation of ERK1/2 and JNK1/2. Treatment with an ERK1/2 inhibitor (PD98059) or JNK1/2 inhibitor (SP600125) enhanced the inhibitory effects of metformin on the migration and invasion of HCC cells. Moreover, metformin-induced inhibition of MMP-9 and uPA promoter activity also blocked the nuclear translocation of NF-κB and its binding to the MMP-9 and uPA promoters, and these suppressive effects were further enhanced by PD98059 or SP600125. Moreover, metformin markedly enhanced the anti-metastatic effects of sorafenib. In conclusion, metformin inhibits the migration and invasion of HCC cells by suppressing the ERK/JNK-mediated NF-κB-dependent pathway, and thereby reducing uPA and MMP-9 expression. Additionally, combination treatment with metformin and sorafenib yielded synergistic inhibitory effects in suppressing cell migration and invasion of HCC cells. These findings provide insight into the molecular mechanisms involved in the anti-metastatic effects of metformin, as well as its ability to enhance the chemosensitivity of HCC cells to sorafenib.
URI:	http://dx.doi.org/10.1007/s00726-014-1838-4 https://ir.csmu.edu.tw:8080/ir/handle/310902500/17971
關聯:	Amino Acids December 2014, Volume 46, Issue 12, pp 2809–2822
显示于类别:	[醫學系] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	211	检视/开启

检视Licence

在CSMUIR中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....