kp372-1 and Adenocarcinoma

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.

Topics: Adenocarcinoma; Aged; Apoptosis; Benzamides; Cell Survival; Cells, Cultured; Cyclohexanones; Drug Synergism; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Lung Neoplasms; Male; Mechanistic Target of Rapamycin Complex 1; Middle Aged; Multiprotein Complexes; Neoplasm Staging; NF-kappa B; Oncogene Protein v-akt; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Sirolimus; Tetrazoles; TOR Serine-Threonine Kinases