Curcumin suppresses MUC5AC production via interfering with the EGFR signaling pathway.

Abstract

Excessive mucin production in the airway may contribute to airway inflammatory diseases. Curcumin has been reported to prevent mucin5AC (MUC5AC) production in human airway epithelial cells; however, the molecular targets of curcumin involved in regulating MUC5AC expression have remained elusive. The present study aimed to elucidate the molecular mechanisms by which curcumin regulates MUC5AC production, utilizing the NCI‑H292 human airway epithelial cell line featuring MUC5AC hypersecretion. Curcumin was able to counteract the endothelial growth factor(EGF)‑stimulated mRNA and protein expression of MUC5AC. In addition, curcumin treatment prevented EGF‑induced phosphorylation of EGF receptor(EGFR) as well as the downstream AKT and signal transducer and activator of transcription3(STAT3), while inhibition of PI3K and STAT3 signaling significantly attenuated the expression of MUC5AC that was induced by EGF. Furthermore, EGF‑induced increases in the levels of phosphorylated STAT3 in the nuclear fraction were inhibited by curcumin and PI3K inhibitors. In addition, treatment with curcumin significantly decreased MUC5AC and EGFR expression in a time‑dependent manner under basal conditions. These results demonstrated that curcumin inhibited MUC5AC protein expression in NCI‑H292 cells under basal conditions as well under EGF stimulation. This inhibition was accompanied by decreased activation of the EGFR/AKT/STAT3 pathway and reduced EGFR expression, which indicated that curcumin may have a dual role in interfering with the EGFR signaling pathway and inhibiting mucin expression in human airway epithelial cells.