Flavonoids inhibitory effect and mechanism on laryngeal carcinoma cell cytotoxicity in AGEs/RAGE/NF-κB pathway

Abstract

Laryngeal carcinoma is a head and neck tumor. Although its survival rate has been improved, some patients die from tumor recurrence or metastasis. This experiment explored the effect and mechanism of flavonoids on laryngeal cancer cell cytotoxicity. Immunohistochemical staining was performed on laryngeal carcinoma tissues. A total of 6 groups were set up in this experiment as follows: the experimental group was added with flavonoids (at 2.5, 5, 10, 20, and 40 mg/L concentrations). Cytotoxicity, proliferation, apoptosis and migration ability were detected respectively. The expressions of Advanced glycation end products (AGEs), receptor for advanced glycation endproducts (RAGE) and Nuclear factor kappa B (NF-κB) proteins were determined. NF-κB/p65 was highly expressed in laryngeal carcinoma tissue cells cytoplasm. The cytotoxicity test proved that, the flavonoids were less toxic to DU4475 and EVC304 cells. After the Hep-2 cells were cultured in vitro for 48 h, as the concentration of flavonoids increased, the cells gradually became round, and their volume and adhesion gradually decreased. The number and density of Hep-2 cells decreased dose and time-dependently. The apoptosis rate and relative wound surface area in experimental group were increased (p <0.05) in a dose-dependent manner. The expressions of AGEs, RAGE and NF-κB in experimental group were decreased (p <0.05). NF-κB/p65 is positively expressed in laryngeal cancer tissues. In conclusion, Flavonoids are less toxic to normal cells and can significantly reduce AGEs, RAGE and NF-κB expressions, also inhibiting Hep-2 cell proliferation. Flavonoids herein significantly inhibited the migration of Hep-2 cells, thus exerting therapeutic effects.