RESUMO
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.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Metaloproteinase 2 da Matriz/biossíntese , Oligopeptídeos/farmacologia , Animais , Produtos Biológicos/farmacologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Modelos Animais de Doenças , Feminino , Humanos , Cininogênio de Alto Peso Molecular/genética , Cininogênio de Alto Peso Molecular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase NeoplásicaRESUMO
OBJECTIVE: To study the anti-lipid peroxidation action of Rosa davurica Pall. fruit. METHODS: The contents of malondialdehyde (MDA) of the tissue homogenate of the liver, heart, kidney, brain and of the red blood cells induced by hydrogen peroxide in mice were measured. The contents of MDA and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of ischemic myocardium of mice were measured. RESULTS: 0.2 g/L Rosa davurica Pall. fruit could decrease significantly the contents of MDA of the all tissue (P < 0.05). Inhibition rate of 6.7 g/L Rosa davurica Pall. fruit on MDA of the red blood cells induced by hydrogen peroxide was 89.2%. Administration of this extraction successively for six days (ig, 2.0 g x kg(-1) x d(-1)) can significantly reduce the content of MDA (P < 0.01) and augment the activities of SOD and GHS-Px (P < 0.05) in the ischemic myocardium of mice. CONCLUSION: Rosa davurica Pall. fruit can significantly prevent the lipid peroxidation.