Hu Xiao-Wen, Meng Dan, Fang Jing
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, China.
Carcinogenesis. 2008 Dec;29(12):2369-76. doi: 10.1093/carcin/bgn244. Epub 2008 Oct 28.
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.
芹菜素是一种常见的膳食类黄酮，已被发现具有抗肿瘤特性，因此在开发癌症化学预防和/或化疗药物方面具有特殊意义。在此，我们证明芹菜素可抑制粘着斑激酶（FAK）的表达以及人卵巢癌A2780细胞的迁移和侵袭。FAK是整合素和生长因子下游的一种非受体蛋白酪氨酸激酶。它在癌细胞的迁移和侵袭中起重要作用。我们发现芹菜素可抑制A2780细胞的粘附、迁移和侵袭。芹菜素通过降低其蛋白质稳定性来减弱FAK的表达。FAK在A2780细胞的迁移和侵袭中起关键作用。FAK的过表达可逆转芹菜素抑制的A2780细胞迁移和侵袭。体内实验表明，芹菜素可抑制接种于裸鼠卵巢的A2780细胞的自发转移。我们的结果为芹菜素抑制卵巢癌的机制提供了新的见解。这些结果表明，芹菜素对FAK的分子靶向作用可能是卵巢癌化学预防和/或化疗的一种有用策略。
