Mefloquine HCl promotes DNA repair and alleviates radiation-induced lung epithelial cell injury

ZHANG Yan; WEN Qingqiu; HUANG Haibo; ZHOU Meijuan; WANG Jianyu

doi:10.12122/j.issn.1673-4254.2026.03.03

Abstract：Objective To investigate the protective effect of mefloquine HCl(MQ)against X-ray irradiation-induced DNA damage in lung epithelial cells.Methods Human lung epithelial cells(BEAS-2B)were divided into blank control group,irradiation group,and irradiation+MQ treatment group.The effects of MQ on cell proliferation and radiosensitivity after X-ray irradiation were assessed using CCK-8 assay,EdU-488 assay,and colony formation assay.Apoptosis and cell cycle distribution of BEAS-2B cells with different treatments were detected by flow cytometry.The effect of MQ in promoting DNA double-strand break(DSB)repair was observed using immunofluorescence staining and comet assay,and the molecule ar mechanism was explored using Western blotting,qPCR,and luciferase reporter assays.Results MQ at 0-10 μmol/L did not significantly affect BEAS-2B cell viability.Compared to the irradiated cells,treatment with 0-10 μmol/L MQ enhanced the cell viability,and the effect was the most conspicuous at 10 μmol/L.MQ treatment obviously promoted proliferation and increased clonogenic survival rate of irradiated BEAS-2B cells while reducing their radiosensitivity,and significantly lowered cell apoptosis rate following the irradiation.Cell cycle analysis revealed that MQ alleviated G2/M phase arrest induced by irradiation,and comet assay and immunofluorescence staining showed reduced comet tail moment and γH2AX foci formation in irradiation+MQ group.Western blotting and qPCR demonstrated that MQ treatment for 48 h significantly increased CtIP promoter activity and upregulated CtIP expressions at both the mRNA and protein levels.Conclusion MQ promotes DSB repair in BEAS-2B cells by upregulating CtIP expression and may thus alleviate radiation-induced lung epithelial cell injury.