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Carcinogenesis Advance Access originally published online on October 28, 2008
Carcinogenesis 2008 29(12):2369-2376; doi:10.1093/carcin/bgn244
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Apigenin inhibited migration and invasion of human ovarian cancer A2780 cells through focal adhesion kinase

Xiao-Wen Hu, Dan Meng and Jing Fang*

Key Laboratory of Nutrition and Metabolism, Institute of Nutritional Sciences, Shanghai Institute for Biological Sciences, The Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China

* To whom correspondence should be addressed. Tel: +86 21 54920241; Fax: +86 21 54920291; Email: jfang{at}sibs.ac.cn

Apigenin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of chemopreventive and/or chemotherapeutic agent for cancers. Here, we demonstrate that apigenin inhibits expression of focal adhesion kinase (FAK) and migration and invasion of human ovarian cancer A2780 cells. FAK is a non-receptor protein tyrosine kinase downstream of integrins and growth factors. It plays an important role in migration and invasion of cancer cells. We found that apigenin inhibited adhesion, migration and invasion of A2780 cells. Apigenin attenuated FAK expression through reducing its protein stability. FAK plays a critical role in migration and invasion of A2780 cells. Overexpression of FAK could reverse A2780 cell migration and invasion inhibited by apigenin. The in vivo experiments showed that apigenin inhibited spontaneous metastasis of A2780 cells implanted onto the ovary of nude mice. Our results provide a new insight into the mechanisms that apigenin inhibits ovarian cancers. These results suggest that molecular targeting of FAK by apigenin might be a useful strategy for chemoprevention and/or chemotherapeutics of ovarian cancers.

Abbreviations: CHX, cycloheximide; ECM, extracellular matrix; FAK, focal adhesion kinase; MG, matrigel; PBS, phosphate-buffered saline; siRNA, small interfering RNA

Received July 4, 2008; revised September 26, 2008; accepted October 20, 2008.


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