Effect of inhibition of Src tyrosine kinase on cell proliferation of NSCLC

OBJECTIVE:To study the effect of inhibition of Src tyrosine kinase on cell proliferation of NSCLC in vitro and in vivo. METHODS: Western blot and immunoprecipitation were used to evaluate the expression and phosphorylation of Src in NSCLC cells. MTT assay was used to examine the effect of inhibition of Src phosphorylation on cell proliferation of NSCLC in vitro. Subcutaneous tumor model induced by PC-9 and A549 cells was used to explore the effect of inhibition of Src tyrosine kinase on cell proliferation of NSCLC in vivo. RESULTS: Src tyrosine kinase was obviously activated,but not over-expression in NSCLC cells. Src tyrosine kinase inhibitor reduced the phosphorylation of Src in a dose-dependent manner in NSCLC cell lines. Submicromolar Src tyrosine kinase inhibitor (3 μmol/L) suppressed the proliferation of PC-9 and A549 cells in a dose dependent manner,P0.05, and 3 μmol/L Src tyrosine kinase inhibitor also suppressed the proliferation of H226 cells significantly, P0.001. For the subcutaneous tumors,after oral feeding with 10 and 50 mg/(kg·d) Src tyrosine kinase inhibitor for 2 weeks,the volume of subcutaneous tumors induced by PC-9 cells were inhibited by 73.28% and 93.4%(P0.001),respectively. While the same treatment was less effective to subcutaneous tumors produced by A549 cells,50 mg/(kg·d) Src tyrosine kinase inhibitor did not cause significant inhibition until treatment 3 weeks later, and the inhibition rate was about 39.4%, P 0.05. CONCLUSION: Inhibition of Src tyrosine kinase could suppress the proliferation of NSCLC cells in vitro and in vivo.