TBK1 inhibitor amlexanox exerts anti-cancer effects against endometrial cancer by regulating AKT/NF-κB signaling

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Endometrial cancer presents challenges, especially in advanced stages.
• TANK-binding kinase 1 (TBK1) is key in inflammation and immunity but its role in endometrial cancer is unclear.
• Investigating TBK1's function is crucial for developing new treatments.

Purpose of the Study:

• To explore the anti-cancer effects of amlexanox, a TBK1 inhibitor, on endometrial cancer.
• To elucidate the underlying molecular mechanisms of amlexanox's action.
• To assess the therapeutic potential of targeting TBK1 in uterine corpus endometrial carcinoma (UCEC).

Main Methods:

• Analyzed TBK1 genetic mutations and expression in endometrial cancer.
• Utilized Kaplan-Meier plotter for prognostic analysis.
• Conducted in vitro experiments (cell proliferation, cell cycle, migration) with TBK1 knockdown and amlexanox.
• Performed xenograft experiments to evaluate tumor growth inhibition.
• Investigated the role of the AKT/NF-κB signaling pathway.

Main Results:

• Low TBK1 expression correlated with a good prognosis in UCEC patients.
• TBK1 knockdown and amlexanox significantly inhibited endometrial cancer cell proliferation, cell cycle progression, and migration.
• The anti-cancer effects were mediated through the AKT/NF-κB signaling pathway.
• Amlexanox treatment and TBK1 knockdown suppressed tumor growth in vivo.

Conclusions:

• Amlexanox demonstrates significant anti-cancer activity against endometrial cancer.
• Targeting TBK1 via amlexanox inhibits cancer progression by modulating the AKT/NF-κB pathway.
• This study supports amlexanox as a potential therapeutic agent for UCEC.