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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

郝一 李译 高明 董雯 胡美茹 宋伦

军事医学2012,Vol.36Issue(4):263-266,4.
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

郝一 1李译 2高明 1董雯 3胡美茹 1宋伦1

作者信息

  • 1. 军事医学科学院基础医学研究所,北京,100850
  • 2. 兰州大学基础医学院病理研究室,兰州,730000
  • 3. 中国药科大学新药筛选中心,南京,210009
  • 折叠

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)

军事医学

OA北大核心CSCDCSTPCD

1674-9960

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