Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-κB inhibition
Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-κB inhibition
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DOI：
10.1038/sj.onc.1203861
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发表时间：
2000-10-05
期刊：
影响因子：
8
通讯作者：
Cheng, GH
中科院分区：
文献类型：
--
作者：
Cheng, QW;Lee, HH;Cheng, GH
在 A549 人肺腺癌细胞中，我们发现 TNF-α 和几种常用化疗药物通过 NF-kappa B 依赖性途径上调 Bcl-x 和/或 Bfl-1/A1 的表达。虽然亲代 A549 细胞对 TNF-α 和化疗药物的细胞毒性作用具有抗性，但 NF-κ B 阻断的 A549 细胞对这两种药物均敏感。 Bcl-x 或 Bfl-1/A1 在 NF-κ B 缺陷细胞中的生理水平表达提供了针对 TNF-α 和化疗治疗的差异性保护。这些研究为化疗引起的化疗耐药现象提供了潜在的机制，也揭示了克服化疗耐药的潜在策略。
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.