The Effect Of Recombinant Human Bone Morphogenetic Protein-2 On Migration And Invasion Ability And Interstitial Collagenase Of Human Hepatoma SMMC-7721 Cells

Objective:To observe the effect of recombinant human bone morphogenetic protein2(rhBMP-2) on migration and invasion ability of human hepatocellular carcinoma SMMC-7721 cells,and the effect of rhBMP-2 on synthesis of interstitial collagenase (MMP-1) in SMMC-7721 cells.Methods:1 The human hepatocellular carcinoma SMMC-7721 cell lines were cultured 24,48,72 hours with rhBMP-2 at various concentrations(0,200,400,600μg/L)of the medium.Detected the migration ability of the cells in vitro by scrification assay and invasive ability by Transwell chamber invasion assay after rhBMP-2 interfered the cells 12,24,48 hours respectively.2 The human hepatocellular carcinoma SMMC-7721 cell lines were cultured 48 hours with rhBMP-2 at various concentrations(0,200,500μg/L)of the medium. Dected the MMP-1 mRNA expression of SMMC-7721 cells by reverse transcription polymerase chain reaction (RT-PCR) and MMP-1 protein expression by western blot.Results:1 The migration rate of the SMMC-7721 cells differed statistical significantly across the varied concentration rhBMP-2 200,400,600μg/L groups and control group after 12,24,48 h respectively(all P<0.05).Difference statistical significantly of the migration rate were also found between groups of rhBMP-2 200,400, 600μg/L (P<0.05).The trans-membrane-cells of the SMMC-7721 cells difference statistical significantly across the varied concentration rhBMP-2 200,400,600μg/L groups and control group after 12,24 and 48 h(all P<0.05).Difference statistical significantly of the trans-membrane-cells were also found between groups of rhBMP-2 200,400, 600μg/L(P<0.05).The migration rate and trans-membrane-cells of the SMMC-7721 cells of the varied concentration rhBMP-2 200,400,600μg/L groups at the time of 12 h differed significantly from the time of 48 h,which were also found between the time of 24 h and 48 h (P<0.05).There were no interaction between concentrations and time.2 The expression of MMP-1 mRNA and protein was highest in rhBMP-2 500μg/L group and lowest in rhBMP-2 0μg/L group, mRNA and protein of rhBMP-2 200μg/L group expressed between these two.Each group statistical significantly (P <0.05). Conclusion:BMP-2 appears to increase the invasion and migration ability of human hepatocellular carcinoma SMMC-7721 cells in a dose-time-dependent pattern. BMP-2 can increase MMP-1 mRNA and protein expression in a concentration- dependent pattern,this may be an important mechanism of BMP-2 upregulating hepatoma invasion and metastasis.