Midazolam regulates the proliferation and migration of lung cancer cells by the EGFR/MER/ERK signaling pathway

MA Weiwei; ZHANG Juanjuan; WEI Jiasen

doi:10.3969/j.issn.1002-7386.2025.06.003

Abstract：Objective To investigate the effects of midazolam(MDZ)on the proliferation,apoptosis and migration of non-small cell lung cancer(NSCLC)cells and its potential mechanisms.Methods Human NSCLC cell lines SK-MES-1 and A549 were cultured in vitro,and the effects of MDZ at varying concentrations on the viability of NSCLC cells were detected by the cell counting kit-8(CCK-8)assay to screen for the appropriate concentration of MDZ.Then,NSCLC cells were induced with blank control,low-dose(100 μmol/L),medium-dose(200 μmol/L)and high-dose MDZ(400 μmol/L),and medium-dose MDZ+EGF(20 ng/mL).Cell proliferation,apoptosis,and migration were examined by EdU assay,flow cytometry and Transwell assay,respectively.Protein levels of key molecules in the epidermal growth factor receptor(EGFR)/mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)signaling pathways were detected by Western blot.Results MDZ dose-dependently inhibited the viability of SK-MES-1 and A549 cells,yielding a nearly 50％of inhibitory rate at 100,200 and 400 μmol/L.Low-dose,medium-dose and high-dose MDZ induction significantly decreased the rate of EdU-positive cells,migratory cell number,pEGFR/EGFR,pMEK/MEK and pERK/ERK,but increased apoptotic rate(P＜0.05).There were no significant differences in the rate of EdU-positive cells,migratory cell number,pEGFR/EGFR,pMEK/MEK and pERK/ERK between NSCLC cells induced with medium-dose and high-dose MDZ(P＞0.05).In comparison to medium-dose MDZ group,NSCLC cells induced with medium-dose MDZ plus EGF had significantly higher rate of EdU-positive cells and migratory cell number,but lower apoptotic rate(P＜0.05).Conclusion Midazolam effectively inhibits the proliferation and migration of NSCLC cells and induces apoptosis by inhibiting the EGFR/MEK/ERK signaling pathway.