期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 355, 期 3, 页码 807-812出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.02.030
关键词
TNF; NF-kappa B; Akt; apoptosis; lung cancer
Blockage of either nuclear factor-kappa B (NF-kappa B) or Akt sensitizes cancer cells to TNF-induced apoptosis. In this study, we investigated the undetermined effect of concurrent blockage of these two survival pathways on TNF-induced cytotoxicity in lung cancer cells. The results show that Akt contributes to TNF-induced NF-kappa B activation in lung cancer cells through regulating phosphorylation of the p65/RelA subunit of NF-kappa B. Although individually blocking IKK or Akt partially suppressed TNF-induced NF-kappa B activation, concurrent suppression of these pathways completely inhibited TNF-induced NF-kappa B activation and downstream anti-apoptotic gene expression, and synergistically potentiated TNIF-induced cytotoxicity. Moreover, suppression of Akt inhibited the Akt-mediated anti-apoptotic pathway through dephosphorylation of BAD. These results indicate that concurrent suppression of NF-kappa B and Akt synergistically sensitizes TNF-induced cytotoxicity through blockage of distinct survival pathways downstream of NF-kappa B and Akt, which may be applied in lung cancer therapy. (c) 2007 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据