Effect of gefitinib on mucus hypersecretion in chronic obstructive pulmonary disease / 中华老年医学杂志

ABSTRACT

Objective To investigate the effect of gefitinib on mucus hypersecretion by inhibiting epidermal growth factor receptor (EGFR) activity in chronic obstructive pulmonary disease (COPD).Methods Human airway epithelail cell lines 16HBE cells were exposed to cigarette smoke extraction (CSE) to establish the COPD model.EGFR activity was inhibited by tyrosine kinase inhibitor gefitinib.The mRNA expressions of EGFR and MUC5AC were detected by real-time PCR.EGFR,p-EGFR and MUC5AC protein levels were determined by Western blot and ELISA.Results EGFR mRNA level was increased by 12.7％ in CSE and 8.6％ in gefitinib group,but had no significant differences among CSE,gefitinib group and control group (all P＞ 0.05).MUC5AC mRNA levels were enhanced by 141.7％,26.4％ in CSE group and gefitinib group respectively,and there were significant differences among CSE,gefitinib group and control group (all P＜0.05).EGFR protein levels were (600.34±64.58) μg/mg,(632.58±72.94) μg/mg,(584.57±67.39) μg/mg,in control,CSE and gefitinib groups,respectively,and there were no significant differences between groups (all P＞0.05).p-EGFR protein levels were (338.62±45.28) μg/mg,(679.43±78.23) μg/mg,(292.74±59.17) μg/mg in control,CSE and gefitinib groups,respectively.MUC5AC protein levels were(72.80±6.25)μg/mg,(187.00±±10.26)μg/mg,(92.57±8.32)μg/mg in control,CSE and gefitinib groups respectively.Compared with control group,p-EGFR and MUC5AC protein levels were increased significantly in CSE group (both P＜0.05),and had no significant differences in p EGFR and MUC5AC protein levels between control group and gefitinib group.Conclusions CSE may lead to mucus hypersecretion through activating the EGFR-mediated signaling pathways.Gefitinib may inhibit mucus hypersecretion by inhibiting EGFR tyrosine kinanse activity.EGFR may serve as a potential target for COPD.