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Correction published on 6 June 2012, see Molecules 2012, 17(6), 6996.

Molecules 2012, 17(2), 1357-1372; doi:10.3390/molecules17021357
Article

GHGKHKNK Octapeptide (P-5m) Inhibits Metastasis of HCCLM3 Cell Lines via Regulation of MMP-2 Expression in in Vitro and in Vivo Studies

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1 Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China 2 Department of Microbial and Biochemical Pharmacy, College of Pharmaceutical Science, Beihua University, Jilin 132001, China 3 Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 5 December 2011 / Revised: 19 January 2012 / Accepted: 27 January 2012 / Published: 2 February 2012
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Abstract

P-5m, an octapeptide derived from domain 5 of HKa, was initially found to inhibit the invasion and migration of melanoma cells. The high metastatic potential of melanoma cells was prevented by the HGK motif in the P-5m peptide in vitro and in an experimental lung metastasis model, suggesting that P-5m may play an important role in the regulation of tumor metastasis. The aim of this study was to measure the effect of P-5m on tumor metastasis of human hepatocarcinoma cell line (HCCLM3) in vitro and in vivo in a nude mouse model of hepatocellular carcinoma (HCC), and detect the mechanisms involved in P-5m-induced anti-metastasis. By gelatin zymography, matrix metallo-proteinases 2 (MMP-2) activity in HCCLM3 was dramatically diminished by P-5m peptide. In addition, the migration and metastasis of HCCLM3 cells was also inhibited by the peptide in vitro. In an orthotopic model of HCC in nude mice, P-5m treatment effectively reduced the lung metastasis as well as the expression of MMP-2 in the tumor tissues. Overall, these observations indicate an important role for P-5m peptide in HCC invasion and metastasis, at least partially through modulation MMP-2 expression. These data suggests that P-5m may have therapeutic potential in metastatic human hepatocarcinoma.
Keywords: GHGKHKNK octapeptide; hepatocellular carcinoma; MMP-2; HCCLM3; cleaved high molecular weight kininogen GHGKHKNK octapeptide; hepatocellular carcinoma; MMP-2; HCCLM3; cleaved high molecular weight kininogen
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Han, X.; Yan, D.-M.; Zhao, X.-F.; Hiroshi, M.; Ding, W.-G.; Li, P.; Jiang, S.; Du, B.-R.; Du, P.-G.; Zhu, X. GHGKHKNK Octapeptide (P-5m) Inhibits Metastasis of HCCLM3 Cell Lines via Regulation of MMP-2 Expression in in Vitro and in Vivo Studies. Molecules 2012, 17, 1357-1372.

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