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A correction was 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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, 2,†,*  and 1,†,*
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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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