Effects of Erythromycin on the Proliferation and Apoptosis of Cultured Nasal Polyp-Derived Cells and the Extracellular Signal-Regulated Kinase (ERK)/Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway
Xiaohua Liu, Xin Wang, Lili Chen, Yuming Shi, Yongjia Wei
(Department of Otolaryngology, Nangang Branch of Heilongjiang Provincial Hospital, Harbin, Heilongjiang, China (mainland))
Med Sci Monit 2018; 24:8048-8055
Erythromycin and its derivatives have been used to treat nasal polyposis and reduce inflammation, but the mechanism of action remains unclear. The extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase (MAPK) pathway proteins are expressed in nasal polyps. The aim of this study was to investigate the effects of erythromycin on cell proliferation, apoptosis, and the expression of p-MEK1 and p-ERK1 on cultured nasal polyp-derived cells.
MATERIAL AND METHODS: Nasal polyp-derived cells (n=32) and control cells from normal inferior turbinate tissue (n=32) were divided into four groups: the control group; the erythromycin-treated (100 μM) group; the selumetinib-treated (2 nM) group; and the erythromycin + selumetinib-treated group. Western blot was used to detect p-MEK1 and p-ERK1 proteins. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect mRNA expression of BCL-2 and BAX. Flow cytometry detected expression of Ki-67 and cell apoptosis. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL). Spectrophotometry assessed caspase-3 activity.
RESULTS: The expression of Ki-67 was significantly increased, and cell apoptosis was significantly reduced in untreated nasal polyp-derived cells compared with controls. Erythromycin treatment significantly decreased cell proliferation and the expression of p-MEK1 and p-ERK1, and increased apoptosis in nasal polyp-derived cells compared with control cells. Selumetinib treatment had a synergistic effect with erythromycin to reduce the expression of p-MEK1 and p-ERK1, reduce cell proliferation, and increase cell apoptosis.
CONCLUSIONS: In cultured cells derived from nasal polyps, erythromycin treatment reduced cell proliferation and increased apoptosis by inhibiting the activation of the ERK/MAPK signaling pathway.
Keywords: Apoptosis, Erythromycin, Nasal Polyps