Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-{kappa}B and Akt pathways
- Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 (United States)
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 TNF-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.
- OSTI ID:
- 20979877
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 355; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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