Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis.
OBJECTIVE
To study the in vitro and in vivo inhibitory effects of genistein on invasive potential of Bel 7402 hepatocellular carcinoma (HCC) cells and to explore the underlying mechanism.


METHODS
Bel 7402 HCC cells were exposed to genistein. The invasive activity of tumor cells was assayed in transwell cell culture chamber. p125FAK expression and cell cycle were evaluated by a functional assay. Cell apoptosis analysis was performed with TUNEL method. In addition, bilateral subrenal capsule xenograft transplantation of HCC was performed in 10 nude mice. Genistein was injected and the invasion of HCC into the renal parenchyma was observed. Microvessels with immunohistochemical staining were detected.


RESULTS
Genistein significantly inhibited the growth of Bel 7402 cells, the inhibitory rate of tumor cells was 26-42%. The invasive potential of Bel 7402 cells in vitro was significantly inhibited, the inhibitory rate was 11-28%. Genistein caused G2/M cell cycle arrest, S phase decreased significantly. The occurrence of apoptosis in genistein group increased significantly. The expression of p125FAK in 5 microg/mL genistein group (15.26+/-0.16%) and 10 microg/mL genistein group (12.89+/-0.36%) was significantly lower than that in the control group (19.75+/-1.12%, P<0.05). Tumor growth in genistein-treated nude mice was significantly retarded in comparison to control mice, the inhibitory rate of tumor growth was about 20%. Genistein also significantly inhibited the invasion of Bel 7402 cells into the renal parenchyma of nude mice with xenograft transplant. The positive unit value of microvessels in genistein-treated group (10.422+/-0.807) was significantly lower than that in control group (22.330+/-5.696, P<0.01).


CONCLUSIONS
Genistein can effectively inhibit the invasive potential of Bel 7402 HCC cells by altering cell cycle, apoptosis and angiogenesis, inhibition of focal adhesion kinase may play a significant role in this process.
Gu
Yan
Y
Department of General Surgery, The Ninth People's Hospital, Shanghai Second Medical University, Shanghai, China. yguchina@ucla.edu
Zhu
Chen-Fang
CF
Iwamoto
Hitoshi
H
Chen
Ji-Sheng
JS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000556:secondary; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019833:Genistein