Abstract
OBJECTIVES: 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. CONCLUSIONS: MQ promotes DSB repair in BEAS-2B cells by upregulating CtIP expression and may thus alleviate radiation-induced lung epithelial cell injury.