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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. May 21, 2008; 14(19): 3054-3058
Published online May 21, 2008. doi: 10.3748/wjg.14.3054
Inhibitory effect of dimeric β peptide on the recurrence and metastasis of hepatocellular carcinoma in vitro and in mice
Song-Mei Wang, Jun Zhu, Luan-Feng Pan, Yin-Kun Liu
Song-Mei Wang, Luan-Feng Pan, Laboratory of Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Jun Zhu, Department of Pharmacy, Shanghai Chest Hospital, Shanghai 200031, China
Yin-Kun Liu, Liver Cancer Institute, Fudan University, Shanghai 200032, China
Correspondence to: Professor Jun Zhu, Department of Pharmacy, Shanghai Chest Hospital, Shanghai 200031, China. jone_zhu@126.net
Telephone: +86-21-62821990-20111
Fax: +86-21-62801109
Received: June 21, 2007
Revised: March 25, 2008
Published online: May 21, 2008
Abstract

AIM: To block the adhesion of tumor cells to the extracellular matrix, and prevent tumor metastasis and recurrence, the dimer of the β peptide (DLYYLMDLSYSMKGGDLYYLMDLSYSMK, β2) was designed and synthesized and its anti-adhesion and anti-invasion effects on hepatocellular carcinoma cells were assessed. Additionally, its influence on the metastasis and recurrence of mouse hepatocellular carcinoma was measured.

METHODS: The anti-adhesion effect of β2 on the highly metastatic hepatocellular carcinoma cell line HCCLM6 cells and fibronectin (FN) was assayed by the MTT assay. The inhibition of invasion of HCCLM6 cells by β2 was observed using a Transwell (modified Boyden chamber) and matrigel. Using the hepatocellular carcinoma metastasis model and LCI-D20 nude mice, the influence of β2 on the metastasis and recurrence of hepatocellular carcinoma after early resection was investigated.

RESULTS: HCCLM6 cells co-incubated with 100 &mgr;mol/L, 50 &mgr;mol/L, 20 &mgr;mol/L or 10 &mgr;mol/L β2 for 3 h showed an obvious decrease in adhesion to FN. The adhesion inhibition ratios were 11.8%, 21.7%, 29.6% and 48.7%, respectively. Additionally, HCCLM6 cells cultured with 100 &mgr;mol/L β2 had a dramatic decrease in cell invasion. β2 was also observed to inhibit the incisal edge recurrence and the distant metastasis of nude mice hepatocellular carcinoma after early resection (P < 0.05).

CONCLUSION: The β2 peptide can specifically block the adhesion and invasion of HCCLM6 cells, and can inhibit HCC recurrence and metastasis of LCI-D20 model posthepatectomy in vivo. Thus, β2 should be further studied as a new anti-tumor drug.

Keywords: β peptide, Hepatocellular carcinoma, Anti-adhesion, Invasion, Metastasis, Recurrence