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World J Gastroenterol. Nov 7, 2005; 11(41): 6512-6517
Published online Nov 7, 2005. doi: 10.3748/wjg.v11.i41.6512
Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis
Yan Gu, Chen-Fang Zhu, Hitoshi Iwamoto, Ji-Sheng Chen
Yan Gu, Chen-Fang Zhu, Department of General Surgery, The Ninth People’s Hospital, Shanghai Second Medical University, Shanghai 200011, China
Hitoshi Iwamoto, Fifth Department of Surgery, Tokyo Medical University, Tokyo 193-8639, Japan
Ji-Sheng Chen, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
Author contributions: All authors contributed equally to the work.
Supported by the Basic Research Key Project of the Science Foundation of Shanghai Municipal Commission of Science and Technology, No. 02JC14001
Correspondence to: Yan Gu, Division of Liver and Pancreas Transplantation, The Dumont-UCLA Transplant Center, Los Angeles, CA 90095, United Stutes. yguchina@ucla.edu
Telephone: +1-323-397-8941
Received: March 18, 2005
Revised: April 8, 2005
Accepted: April 11, 2005
Published online: November 7, 2005
Abstract

AIM: 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 μg/mL genistein group (15.26±0.16%) and 10 μg/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).

CONCLUSION: 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.

Keywords: Genistein; Human hepatocellular carcinoma; Invasion; Cell cycle; Apoptosis; Angiogenesis