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GHGKHKNK Octapeptide (P-5m) Inhibits Metastasis of HCCLM3 Cell Lines via Regulation of MMP-2 Expression in in Vitro and in Vivo Studies
Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China
Department of Microbial and Biochemical Pharmacy, College of Pharmaceutical Science, Beihua University, Jilin 132001, China
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; in revised form: 19 January 2012 / Accepted: 27 January 2012 / Published: 2 February 2012
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
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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.
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(2):1357-1372.
Han, Xiao; Yan, Dong-Mei; Zhao, Xiang-Feng; Hiroshi, Matsuura; Ding, Wei-Guang; Li, Peng; Jiang, Shuang; Du, Bai-Rong; Du, Pei-Ge; Zhu, Xun. 2012. "GHGKHKNK Octapeptide (P-5m) Inhibits Metastasis of HCCLM3 Cell Lines via Regulation of MMP-2 Expression in in Vitro and in Vivo Studies." Molecules 17, no. 2: 1357-1372.