Activation of Akt involves resistance to NF-κB inhibition and abrogation of both triggers synergistic apoptosis in lung adenocarcinoma cells
Copyright policy )Activation of Akt involves resistance to NF-κB inhibition and abrogation of both triggers synergistic apoptosis in lung adenocarcinoma cells
Although nuclear factor (NF)-κB and phosphoinositide 3-kinase (PI3K)-Akt-mTOR comprise key pathways, their interrelationship in lung cancer cell survival is poorly understood and needs further analyses.We examined the activation of the NF-κB and Akt-mTORC1-p70 S6 kinase (S6K) pathways and the effect of inhibitors for NF-κB, mTORC1, and Akt using fresh lung adenocarcinoma cells.The cases used for this study showed constitutive NF-κB activity; however, all cases but one showed resistance to NF-κB inhibition. Further examination revealed that the resistant cases were also active in the Akt-mTORC1-S6K pathway. These cases were insensitive to mTORC1 inhibition but sensitive to Akt inhibition. Akt inhibition recovered sensitivity to NF-κB inhibition and dual inhibition showed a synergistic effect on apoptosis induction.These results indicate that the activation of Akt involves resistance to NF-κB inhibition and both pathways synergistically support the survival of lung adenocarcinoma cells. The results also indicate that inhibition of the mTORC1-S6K pathway does not inhibit the survival of these cells.
- Tohoku University Japan
- Aichi Medical University Japan
- Toho University Japan
- Kitasato University Japan
Male, Lung Neoplasms, Cell Survival, Cyclohexanones, NF-kappa B, Ribosomal Protein S6 Kinases, 70-kDa, Apoptosis, Drug Synergism, Adenocarcinoma, Mechanistic Target of Rapamycin Complex 1, Middle Aged, Heterocyclic Compounds, 4 or More Rings, Oncogene Protein v-akt, Multiprotein Complexes, Benzamides, Humans, Female, Cells, Cultured, Aged, Neoplasm Staging
Male, Lung Neoplasms, Cell Survival, Cyclohexanones, NF-kappa B, Ribosomal Protein S6 Kinases, 70-kDa, Apoptosis, Drug Synergism, Adenocarcinoma, Mechanistic Target of Rapamycin Complex 1, Middle Aged, Heterocyclic Compounds, 4 or More Rings, Oncogene Protein v-akt, Multiprotein Complexes, Benzamides, Humans, Female, Cells, Cultured, Aged, Neoplasm Staging
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