Src激酶抑制剂ZD6474在乳腺癌MCF-7细胞转移中的作用和机制  

Effects and mechanisms of Src kinase inhibitor ZD6474 in metastasis of human breast cancer MCF- 7 cells

作　　者：赵剑平[1] 尹培[1] 刘春海[1] 吕佰瑞[1] 柴鹏[1] 

机构地区：[1]邯郸市中心医院核医学科,河北邯郸056001

出　　处：《现代肿瘤医学》2016年第1期12-15,共4页Journal of Modern Oncology

基　　金：河北省卫生厅科研基金项目(编号:ZD20140114)

摘　　要：目的:探讨Src激酶抑制剂ZD6474在乳腺癌MCF-7细胞转移中的作用和机制。方法:乳腺癌MCF-7细胞经ZD6474处理后,检测肿瘤细胞体外黏附、侵袭能力的改变,应用Western blot及Real-time PCR观察细胞Src激酶磷酸化水平及E-钙黏素和β-连环蛋白表达的变化,报告基因技术检测Snail在转录水平表达的变化。结果:ZD6474可抑制MCF-7细胞中Src激酶活性,在ZD6474浓度为1×10^(-5)mol/L和1×10^(-4)mol/L时,细胞的抑制率分别为12.2%和27.5%。Src酪氨酸激酶抑制剂可上调E-cadherin在mRNA和蛋白表达水平,下调β-catenin在mRNA和蛋白表达水平及Snail启动子活性。结论:Src激酶与乳腺癌MCF-7细胞肿瘤转移能力密切相关,阻断Src激酶活性可抑制肿瘤细胞转移能力。Objective：To investigate the effects of Src kinase inhibitor ZD6474 in the metastasis of human breast cancer MCF - 7 cells and its related mechanisms. Methods： MCF - 7 cells were treated with ZD6474 to detect the changes in cell adhesion and invasion. Western blot assay and Real -time PCR were used to examine the expression of Src, E - cadherin and β - catenin at mRNA and protein level, reporter genes assay was used to examine the transcriptional activity of Snail. Results ： ZD6474 could down regulate Src activities in MCF - 7 cells. After these cells were treated with ZD6474, the inhibition rate was 12.2% and 27.5% when the MCF - 7 cells were treated with ZD6474 at the concentrations of 1× 10-5mol/L and 1× 10-4mol/L. Src tyrosine kinase inhibitor obviously increased the expression of E - cadherin at protein and mRNA levels, and decreased the expression of β - catenin at protein and mRNA levels, transcriptional activity of Snail. Conclusion： A close relationship was found between Src kinase and the metastasis potential of human breast cancer MCF -7 cells. The inhibition of Src kinase activity could suppress tmnor metastasis.

关 键 词：Src激酶抑制剂 肿瘤转移 乳腺癌 

分 类 号：R730[医药卫生—肿瘤] R737.9[医药卫生—临床医学]