Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma

被引:52
作者
Gu, Yan [1 ]
Zhu, Cheng-Fang [1 ]
Dai, Ya-Lei [2 ]
Zhong, Qiang [1 ]
Sun, Bo [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Dept Gen Surg, Shanghai Hosp 9, Shanghai 200011, Peoples R China
[2] Tongji Univ, Sch Med, Dept Immunol, Shanghai 200092, Peoples R China
关键词
Human hepatocellular carcinoma; Genistein; Metastasis; CELL-LINES; SOY ISOFLAVONE; ESTABLISHMENT; APOPTOSIS; RELEVANT; TUMOR; GENE;
D O I
10.3748/wjg.15.4952
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
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 mu g/mL and 20 mu g/mL genistein-treated groups. Genistein caused G(0)/G(1) 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. (C) 2009 The WJG Press and Baishideng. All rights reserved.
引用
收藏
页码:4952 / 4957
页数:6
相关论文
共 27 条
[1]
Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells [J].
Agochiya, M ;
Brunton, VG ;
Owens, DW ;
Parkinson, EK ;
Paraskeva, C ;
Keith, WN ;
Frame, MC .
ONCOGENE, 1999, 18 (41) :5646-5653
[2]
Flavonoid effects relevant to cancer [J].
Brownson, DM ;
Azios, NG ;
Fuqua, BK ;
Dharmawardhane, SF ;
Mabry, TJ .
JOURNAL OF NUTRITION, 2002, 132 (11) :3482S-3489S
[3]
Genistein affests hepatoma cells at G2/M phase:: involvement of ATM activation and upregulation of p21waf1/cip1 and Wee1 [J].
Chang, KL ;
Kung, ML ;
Chow, NH ;
Su, SJ .
BIOCHEMICAL PHARMACOLOGY, 2004, 67 (04) :717-726
[4]
Chiu JH, 1996, CANCER DETECT PREV, V20, P43
[5]
Inhibition of cell proliferation and induction of apoptosis by genistein in experimental hepatocellular carcinoma [J].
Chodon, Dechen ;
Banu, S. Mumtaz ;
Padmavathi, R. ;
Sakthisekaran, D. .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2007, 297 (1-2) :73-80
[6]
Genistein [J].
Dixon, RA ;
Ferreira, D .
PHYTOCHEMISTRY, 2002, 60 (03) :205-211
[7]
Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters [J].
Entschladen, F ;
Drell, TL ;
Lang, K ;
Joseph, J ;
Zaenker, KS .
LANCET ONCOLOGY, 2004, 5 (04) :254-258
[8]
Gu Y, 2003, ZHONGHUA SHIYAN WAIK, V20, P4
[9]
Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis [J].
Gu, Yan ;
Zhu, Chen-Fang ;
Iwamoto, Hitoshi ;
Chen, Ji-Sheng .
WORLD JOURNAL OF GASTROENTEROLOGY, 2005, 11 (41) :6512-6517
[10]
Hilakivi-Clarke L, 2007, CURR CANCER DRUG TAR, V7, P465