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.