摘要
目的:研究非小细胞肺癌细胞株A549中表皮生长因子受体(EGFR)和CXCR4之间的关系。方法:用不同浓度(20,40,60μg/L)的表皮生长因子(EGF)处理血清饥饿的A549细胞24 h,RT-PCR检测CXCR4 mRNA;血清饥饿的A549细胞用AG1478(EGFR磷酸化特异性抑制剂,10μmol/L)处理24 h,分别用RT-PCR和Westernblot检测CXCR4 mRNA和蛋白表达水平;分别在有/无LY294002(PI-3K通路抑制剂)情况下,用EGF处理血清饥饿的A549细胞,检测CXCR4 mRNA水平。结果:EGF使非小细胞肺癌细胞CXCR4表达上调约3-4倍,EGFR磷酸化抑制剂AG1478能降低CXCR4表达,EGF通过PI-3K信号通路上调CXCR4表达且CXCR4 mRNA含量以浓度依赖的方式增加。结论:EGF通过EGFR和PI-3K信号通路上调CXCR4表达,CXCR4和EGFR胞内信号通路之间的交互作用可能促进肿瘤进展,对于协同表达CXCR4和EGFR的非小细胞肺癌患者,同时抑制EGFR和CXCR4可能是潜在的治疗靶点。
Objective： To study the relationship between EGFR and CXCR4 in non-small cell lung cancer cell line A549.Methods： Serum-starved A549 cells were stimulated with different concentration of EGF（20 μg/L,40 μg/L,and 60 μg/L） for 24 hours and then CXCR4 expression levels were evaluated by real time PCR.Serum starved A549 cells were treated with AG1478（specific inhibitor of EGFR phosphorylation）（10 μmol/L） for 24 h,CXCR4 expression were re-evaluated by real-time PCR and Western blot.Serum-starved A549 cells were treated with EGF in the presence or absence of LY294002（PI-3 kinase pathway inhibitor） to investigate the changes of CXCR4 mRNA levels.Results： EGF up-regulated CXCR4 expression about 3 to 4 folds.CXCR4 expression was reduced after treatment with EGFR phosphorylation inhibitor（AG1478）.EGF induced up-regulation of CXCR4 is enhanced through PI-3 kinase pathway,and CXCR4 mRNA up-regulation increased in a concentration-dependant manner.Conclusion： EGF up-regulates the CXCR4 expression through PI-3K signaling pathway,and this interaction between CXCR4 and EGFR intracellular signaling pathways may contribute to tumor progression.Inhibition of both EGFR and CXCR4 may be potential therapeutic targets for NSCLC patients who have concomitant over expression of CXCR4 and EGFR.
出处
《武汉大学学报（医学版）》
CAS
北大核心
2012年第6期775-778,共4页
Medical Journal of Wuhan University
基金
湖北省自然科学基金资助项目(编号:2008CDA065)
