Inhibitory effects of genistein on metastasis of human hepatocellular carcinoma.
OBJECTIVE
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 microg/mL and 20 microg/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).


CONCLUSIONS
Genistein appears to be a promising agent in the inhibition of metastasis of hepatocellular carcinoma.
Department of General Surgery, Shanghai Ninth Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. yangu@sjtu.edu.cn
Yan
Y
Gu
Cheng-Fang
CF
Zhu
Ya-Lei
YL
Dai
Qiang
Q
Zhong
Bo
B
Sun
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019833:Genistein; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human