NF-κB is activated in a variety of human cancers. However, its role in osteosarcoma (OS) remains unknown. Here, we have elucidated the implication of NF-κB in the oncogenic phenotype of OS tumor cells. We reported that activation of NF-κB was a common event in the human OS. Inhibition of NF-κB using inhibitor Bay 11-7085 repressed proliferation, survival, migration, and invasion but increased apoptosis in 143B and MG63 OS cells, indicating that NF-κB is critically implicated in the oncogenesis of OS. Notably, Bay 11-7085 not only inactivated NF-κB but also reduced the phosphorylation of AKT via its induction of PTEN, suggesting the existence of a novel NF-κB/PTEN/PI3K/AKT axis. In vivo, Bay 11-7085 suppressed tumor growth in the bone by targeting NF-κB and AKT. Interestingly, combined treatment with Bay 11-7085 and the PI3K inhibitor, LY294002, triggered an augmented antitumor effect. Our results demonstrate that NF-κB potentiates the growth and aggressiveness of OS. Pharmacological inhibition of NF-κB represents a promising therapy for the treatment of OS.

• Klíčová slova
• Bay 11-7085 Sigma-Aldrich,
• MeSH
• cílená molekulární terapie MeSH
• dimethylsulfoxid terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední NOD MeSH
• nádorové buňky kultivované účinky léků   MeSH
• NF-kappa B účinky léků   MeSH
• nitrily farmakologie   terapeutické užití   MeSH
• osteosarkom * farmakoterapie   genetika   patologie   MeSH
• polymerázová řetězová reakce metody   MeSH
• protoonkogenní proteiny c-akt antagonisté a inhibitory   genetika   metabolismus   MeSH
• RNA nádorová izolace a purifikace   účinky léků   MeSH
• sulfony farmakologie   terapeutické užití   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH