抑制Src酪氨酸激酶对非小细胞肺癌细胞VEGF表达的影响

摘要

Objective:To study the effect of Src tyrosine kinase inhibition on VEGF expression in NSCLC cells. Methods: ELISA was used to examine the level of VEGF expression in NSCLC cells and the effect of Src tyrosine kinase inhibition on VEGF expression in NSCLC cells. For the subcutaneous tumor model and lung metastasis model, NSCLC cells were inoculated into NK cell - depleted male SCID mice by subcutaneous injection and via the tail vein, respectively. Immunohistochemistry was used to test the effect of Src tyrosine kinase inhibition on VEGF expression in subcutaneous tumor and lung metastasis in mice. Results: There was VEGF expression in all 3 NSCLC cells in our experiment. 0.lμmol/L,0. 3μmol/L, 1 μmol/L and 3μmol/L Src tyrosine kinase inhibitor suppressed VEGF expression in H226 cells by 18% ,8% ,24% and 47%. 0. Lμmol/L,0. 3μmol/L,lμmo]/L and 3μmol/L Src tyrosine kinase inhibitor suppressed VEGF expression in PC - 9 cells and A549 cells by 25% ,56% ,51% ,71% and 14% , 23% ,50% , 43% , respectively. Src tyrosine kinase inhibition greatly reduced VEGF expression in subcutaneous tumors and lung metastases produced by NSCLC cells. Conclusion: Src tyrosine kinase inhibition could suppress VEGF expression in NSCLC cells in vitro and in vivo.%目的:探讨抑制Src酪氨酸激酶对非小细胞肺癌细胞VEGF表达的影响.方法:采用ELISA法检测非小细胞肺癌细胞株培养上清中VEGF表达以及抑制Src酪氨酸激酶对VEGF表达的影响;采用雄性严重联合免疫缺陷(SCID )小鼠,敲除NK细胞,建立非小细胞肺癌细胞诱导的皮下肿瘤和实验性肺转移瘤动物模型,采用免疫组化法研究抑制Src酪氨酸激酶对皮下肿瘤和肺转移瘤中VEGF表达的影响.结果:本实验采用的3种非小细胞肺癌细胞都表达VEGF.0.1μmol/L、0.3μmol/L、1μmol/L和3μmol/L Src酪氨酸激酶抑制剂对H226细胞VEGF表达的抑制率分别为18%、8%、24%和47%,对A549细胞VEGF表达的抑制率分别为14%、23%、50%和43%,对PC-9细胞VEGF表达的抑制率分别为25%、56%、51%和71%.抑制Src酪氨酸激酶明显抑制VEGF在肺转移瘤和皮下肿瘤中的表达.结论:抑制Src酪氨酸激酶能够抑制非小细胞肺癌细胞体外和体内VEGF的表达.