Effect of Src tyrosine kinase inhibition on pulmonary metastasis tumor in mice

Objective:To study the effect of Src tyrosine kinase inhibition on pulmonary metastasis tumor in mice and its mechanism.Methods: For lung metastasis model,A549 cells were injected into NK cell-depleted SCID mice via the tail vein.Mice were orally given every day with or without Src tyrosine kinase inhibitor to examine the effect of Src tyrosine kinase inhibition on experimental lung metastasis.Immunohistochemistry was used to test the effect of Src tyrosine kinase inhibition on proliferation index(Ki67 staining) and microvessel density(CD31 staining) of experimental lung metastasis in mice.Results: A549 cells developed numerous small lesions on the surface of the lung in 3 groups,but the nodules of lung in 50mg/kg/d group was smaller than that of control group,representing significantly less lung weight compared to control group and 50mg/kg/d group(P0.05).Treatment with 10mg/kg/d Src tyrosine kinase inhibitor had no significant effect on the lung weight.Treatment with Src tyrosine kinase inhibitor did not cause weight loss of mice significantly,however,inoculated A549 cells 35 days later,the wight in control group was significantly loss(P0.01).Treatment with 50mg/kg/d M475271 not only reduced the number and the size of metastatic lesions,but also inhibited the number of Ki67-positive proliferating tumor cells in lung metastases produced by A549 cells(P0.001).Conclusion: Src tyrosine kinase inhibition could suppress the progression of lung metastasis by the inhibition of local cell proliferation and invasion of A549 cells.