Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-κB inhibition

被引：92
作者：
Cheng, QW
Lee, HH
Li, Y
Parks, TP
Cheng, GH [1 ]
机构：
[1] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[3] CuraGen Corp, New Haven, CT 06511 USA
[4] Cellegy Pharmaceut Inc, S San Francisco, CA 94080 USA
来源：
ONCOGENE | 2000年 / 19卷 / 42期
关键词：
NF-kappa B; Bcl-x; Bfl-1; chemoresistance; chemosensitization;
D O I：
10.1038/sj.onc.1203861
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In A549 human lung adenocarcinoma cells, we found that TNF-alpha and several commonly used chemotherapeutic agents upregulated the expression of Bcl-x and/or Bfl-1/A1 through an NF-kappa B-dependent pathway. While parental A549 cells were resistant to the cytotoxic effects of both TNF-alpha and chemotherapy agents, NF-kappa B-blocked A549 cells were sensitized to both. Expression of either Bcl-x or Bfl-1/A1 in the NF-kappa B-deficient cells at physiological levels provided differential protection against TNF-alpha and chemotherapeutic treatment. These studies provide a potential mechanism for the phenomenon of chemotherapy-induced chemoresistance, and also reveal a potential strategy by which chemoresistance can be overcome.
引用
收藏
页码：4936 / 4940
页数：5
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