3-Hydroxyflavone inhibits the cytotoxicity of oral squamous cell carcinoma cells through the AGEs/RAGE/NF-κB signaling pathway.

BACKGROUND

Advanced glycation end products (AGEs) and their receptor receptor for AGEs (RAGE) promote tumor progression via activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Although 3-Hydroxyflavone exhibits anticancer properties, its role in oral squamous cell carcinoma (OSCC) and its interaction with the AGEs/RAGE/NF-κB axis remain unclear.

OBJECTIVES

This study investigated whether 3-Hydroxyflavone inhibits OSCC by modulating miR-142-5p within the AGEs/RAGE/NF-κB axis.

METHODS

The expression of p65 and miR-142-5p was analyzed in both OSCC tissues and Tca8113 cells. TargetScan prediction and dual-luciferase reporter assays confirmed that p65 is a direct target of miR-142-5p. The effects of 3-Hydroxyflavone on OSCC cells were evaluated using MTT and colony formation assays. Additionally, immunohistochemistry was performed to assess p65 expression in tumor tissues, and Kaplan-Meier analysis was used to evaluate patient survival.

RESULTS

OSCC tissues showed increased p65 nuclear translocation and decreased miR-142-5p levels. The miR-142-5p directly inhibited p65. The 3-Hydroxyflavone treatment suppressed OSCC cell proliferation and colony formation by upregulating miR-142-5p and inhibiting the AGEs/RAGE/NF-κB pathway. High p65 expression correlated with poor survival, while 3-Hydroxyflavone treatment reduced p65 and improved survival.

CONCLUSION

The 3-Hydroxyflavone inhibits OSCC proliferation and enhances survival by upregulating miR-142-5p, which suppresses AGEs/RAGE/NF-κB signaling, suggesting a novel therapeutic strategy.