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Int. J. Mol. Sci. 2012, 13(6), 7271-7282; doi:10.3390/ijms13067271

Oral Administration of Apigenin Inhibits Metastasis through AKT/P70S6K1/MMP-9 Pathway in Orthotopic Ovarian Tumor Model

1 State Key Lab of Reproductive Medicine, and Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, 210029, China 2 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 27 April 2012 / Revised: 28 May 2012 / Accepted: 29 May 2012 / Published: 13 June 2012
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Apigenin, a flavonoid commonly present in the daily diet, is known for its potential anti-tumor properties. However, the effect of apigenin via oral administration on tumor growth and metastasis remains unknown. In this study we developed an orthotopic ovarian tumor model in nude mice to test the effect of apigenin oral administration, and showed that apigenin inhibited the micrometastasis of cancer cells in the animal tumor model. To understand the mechanism of apigenin in inhibiting metastasis, we found that apigenin greatly inhibited MMP-9 expression and p-AKT and p-p70S6K1 levels in the tumor tissues compared to the control group. We further demonstrated that the downregulation of MMP-9 by apigenin was mediated by the AKT/p70S6K1 pathway. These findings help to address the question with common interests to the public of whether oral uptake of flavonoids is effective in preventing cancer. Our results demonstrate for the first time that oral uptake of apigenin can inhibit tumor metastasis through MMP-9 expression using the orthotopic ovarian tumor model.
Keywords: apigenin; orthotopic ovarian cancer model; metastasis; MMP-9 apigenin; orthotopic ovarian cancer model; metastasis; MMP-9
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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He, J.; Xu, Q.; Wang, M.; Li, C.; Qian, X.; Shi, Z.; Liu, L.-Z.; Jiang, B.-H. Oral Administration of Apigenin Inhibits Metastasis through AKT/P70S6K1/MMP-9 Pathway in Orthotopic Ovarian Tumor Model. Int. J. Mol. Sci. 2012, 13, 7271-7282.

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