Anti-tumor effect and the mechanism of a novel antibody targeting EGFR dimer
Objective:To investigate the inhibitory effect and the mechanism of EGFR dimer 5G9,a new antibody against epidermal growth factor receptor(EGFR)dimer interface,on the growth of cancer cells.Methods:Three cell lines with different expression levels of EGFR were selected for this experiment.MTT assay was used to detect the inhibitory effect of the monoclonal antibody EGFR dimer 5G9 on the growth of the three cell lines in vitro.A431 cells were selected as the model of EGFR overexpression to study the effect of monoclonal antibody EGFR dimer 5G9 on EGFR phosphorylation.The tumor inhibition experiment in vivo was carried out in BALB/c mice bearing human epidermal squamous cell carcinoma.Results:EGFR was expressed in low level in NIH-3T3 cells,but overexpressed in BxPC-3 cells and A431 cells.The growth inhibitory rates of monoclonal antibody EGFR dimer 5G9 on BxPC-3 cells and A431 cells were(50.17±0.75)%and(47.09±0.94)%,respectively,but it had no significant inhibitory effect on NIH-3T3 cells.The phosphorylation levels of EGFR in A431 cells were down-regulated by monoclonal antibody EGFR dimer 5G9 combined with epidermal growth factor 2 h later,and was significantly inhibited 12 h later.In vivo anti-tumor test showed that the average tumor volume in the monoclonal antibody EGFR dimer 5G9 administration group and control group were(1 726±187.6)mm3 and(3 082.5±276.1)mm3,respectively.The average tumor wet weights were(1.31±0.13)and(2.33±0.08)g,respectively.Monoclonal antibody EGFR dimer 5G9 had significant tumor inhibition effect in vivo,and the tumor inhibition rate reached 43.78%.Conclusion:EGFR dimer 5G9,a novel antibody targeting EGFR dimer,can exert influence on EGFR signaling pathway by inhibiting the phosphorylation of EGFR,thus effectively inhibit the growth of tumor overexpressing EGFR.
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万方数据
维普
