军事医学2012,Vol.36Issue(4):263-266,4.
三氧化二砷通过抑制IKK/NF-κB信号通路活化发挥促乳腺癌细胞凋亡效应
Arsenic trioxide induces apoptosis in MCF7 human breast cancer cells by inhibiting IKK/NF-κB pathway activation
摘要
Abstract
Objective To explore the role of IKK/NF-kB signaling pathway in mediating the apoptotic effect in human breast cancer cells exposed to arsenic trioxide (arsenite, As2O3). Methods MCF7 cells were treated with arsenite. Cell death was detected by phenol blue staining. Luciferase assay was used to detect the transactivation status of NF -kB in the MCF7 cells. The expression levels of IKKa, IKKP,I-kB and the cytoplasmic/nuclear distribution of p65 and p50 were detected by Western blotting. The expression levels of NF-kB downstream target genes were determined by RT-PCR. Results Arsenite induced apoptosis in MCF7 cells, along with significant inhibition of NF -kB transactivation and NF-kB target genes expression. Interestingly, the expression level of I-kB and cytoplasmic/nuclear distribution of p65 and p50 were not altered, but both IKKa and IKKp levels were dramatically down-regulated under the same conditions. Moreover, overexpressed IKKa or IKKp recovered NF-kB transactivation, and antagonized arsenite induced apoptotic response in MCF7 cells. Conclusion Arsenite induces apoptosis in MCF7 cells by inhibiting IKKs expression and the subsequent NF -kB transactivation.关键词
IKK/NF-κB途径/三氧化二砷/细胞凋亡/乳腺癌细胞Key words
IKK/NF-kB / arsenite/ apoptosis/ breast cancer cells分类
医药卫生引用本文复制引用
郝一,李译,高明,董雯,胡美茹,宋伦..三氧化二砷通过抑制IKK/NF-κB信号通路活化发挥促乳腺癌细胞凋亡效应[J].军事医学,2012,36(4):263-266,4.基金项目
国家自然科学基金资助项目(30871277,30970594,31171342) (30871277,30970594,31171342)
北京市自然科学基金资助项目(5092022,5102035) (5092022,5102035)
国家973计划资助项目(2011CB503803) (2011CB503803)