Brief Article
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 21, 2009; 15(39): 4952-4957
Published online Oct 21, 2009. doi: 10.3748/wjg.15.4952
Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma
Yan Gu, Cheng-Fang Zhu, Ya-Lei Dai, Qiang Zhong, Bo Sun
Yan Gu, Cheng-Fang Zhu, Qiang Zhong, Bo Sun, Department of General Surgery, Shanghai Ninth Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Ya-Lei Dai, Department of Immunology, Tongji University School of Medicine, Shanghai 200092, China
Author contributions: Gu Y and Zhu CF contributed equally to this work; Gu Y and Dai YL designed the research; Zhu CF, Zhong Q and Sun B performed the research; Gu Y and Zhu CF analyzed the data and wrote the paper; Dai YL corrected the manuscript.
Supported by Grants From Shanghai Municipal Health Bureau, No. 054052 and Shanghai Municipal Commission of Science and Technology, No. 02JC14001
Correspondence to: Dr. Yan Gu, Department of General Surgery, Shanghai Ninth Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. yangu@sjtu.edu.cn
Telephone: +86-21-23271025 Fax: +86-21-63131312
Received: August 2, 2009
Revised: August 31, 2009
Accepted: September 7, 2009
Published online: October 21, 2009
Abstract

AIM: To investigate the inhibitory effects of genistein on metastasis of MHCC97-H hepatocellular carcinoma cells and to explore the underlying mechanism.

METHODS: MHCC97-H hepatocellular carcinoma cells were exposed to genistein. A cell attachment assay was carried out in a microculture well pre-coated with fibronectin. The invasive activity of tumor cells was assayed in a transwell cell culture chamber, and cell cycle and apoptosis were evaluated by a functional assay. In addition, the expression and phosphorylation of FAK were detected by Western blotting. In situ xenograft transplantation of hepatocellular carcinoma was performed in 12 nude mice and lung metastasis of hepatocellular carcinoma was observed.

RESULTS: Genistein significantly inhibited the growth of MHCC97-H cells in vitro. Adhesion and invasiveness of MHCC97-H cells were inhibited in a concentration-dependent fashion, and the inhibitory effect of genistein was more potent in the 10 μg/mL and 20 μg/mL genistein-treated groups. Genistein caused G0/G1 cell cycle arrest, an S phase decrease, and increased apoptosis. The expression and phosphorylation of FAK in MHCC-97H cells were significantly decreased. In situ xenograft transplantation of hepatocellular carcinoma was also significantly suppressed by genistein. The number of pulmonary micrometastatic foci in the genistein group was significantly lower compared with the control group (12.3 ± 1.8 vs 16.6 ± 2.6, P < 0.05).

CONCLUSION: Genistein appears to be a promising agent in the inhibition of metastasis of hepatocellular carcinoma.

Keywords: Human hepatocellular carcinoma, Genistein, Metastasis