Abstract
In A549 human lung adenocarcinoma cells, we found that TNF-α and several commonly used chemotherapeutic agents upregulated the expression of Bcl-x and/or Bfl-1/A1 through an NF-κB-dependent pathway. While parental A549 cells were resistant to the cytotoxic effects of both TNF-α and chemotherapy agents, NF-κB-blocked A549 cells were sensitized to both. Expression of either Bcl-x or Bfl-1/A1 in the NF-κB-deficient cells at physiological levels provided differential protection against TNF-α 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.
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HH Lee is supported by a UCLA MSTP Training Grant (GM 08042).
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Cheng, Q., Lee, H., Li, Y. et al. Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-κB inhibition. Oncogene 19, 4936–4940 (2000). https://doi.org/10.1038/sj.onc.1203861
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DOI: https://doi.org/10.1038/sj.onc.1203861
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