Abstract:Objective To investigate the effect of 8-bromo-7-methoxychrysin (BrMC) on chemotherapy sensitivity of cisplatin (DDP)-resistant lung adenocarcinoma cells and its molecular mechanism. Methods A549/DDP cells were cultured with BrMC at different concentrations (2.5, 5, 10 μmol/L), the cell survival rate and apoptosis rate were detected by CCK-8 method and flow cytometry, respectively, the expression of methyl transferase-like 3 (METTL3) in cells was detected by RT-qPCR and Western Blot. A549/DDP cells were treated with DDP at different concentrations (0, 4, 8, 16, 32 μg/mL), A549/DDP cells were treated with different concentrations (0, 4, 8, 16, 32 μg/mL) of DDP and BrMC, and the cell survival rate was detected by CCK-8 method. A549/DDP cells were divided into control group, BrMC group (5 μmol/L BrMC cultured A549/DDP cells), BrMC+NC group (5 μmol/L BrMC cultured A549/DDP cells transfected with negative control plasmid), BrMC+METTL3 group (5 μmol/L BrMC cultured A549/DDP cells transfected with pcDNA3.1-METTL3 plasmid), in addition, 16 μg/mL DDP was added into the cells of each group for treatment, after 48 h, the expression of METTL3 in the cells was detected by RT-qPCR and Western Blot, the cell survival rate was detected by CCK-8 method, and the cell apoptosis rate was detected by flow cytometry, the expression of P-glycoprotein (P-gp) and multi-drug resistance associated protein 1 (MRP1) were detected by Western Blot. Results Compared with the control group, the survival rate of A549/DDP cells cultured with BrMC at different concentrations (2.5, 5, 10 μmol/L) was significantly decreased and the apoptosis rate was significantly increased (P<0.05), the relative mRNA and protein expression levels of METTL3 was significantly decreased (P<0.05). Compared with A549/DDP cells treated with different concentrations (0, 4, 8, 16, 32 μg/mL), the survival rate of A549/DDP cells treated with different concentrations (0, 4, 8, 16, 32 μg/mL) and added with 5 μmol/L BrMC was significantly decreased (P<0.05). In addition, compared with BrMC group, the relative expression levels of METTL3 mRNA and protein, the cell survival rate in BrMC+METTL3 group were significantly up-regulated (P<0.05), and the cell apoptosis rate was significantly decreased (P<0.05), the relative expression levels of P-GP and MRP1 protein were significantly up-regulated (P<0.05). Conclusion BrMC can enhance the sensitivity of DDP resistant lung adenocarcarcinoma cells to DDP by down-regulating METTL3 expression