The mechanism of 5-fluorouracil combined with oxaliplatin on cisplatin resistance in non-small cell lung cancer through microRNA-92a/Wnt/β-catenin pathway

Ye Lijing; Li Yuling; Cao Zhuo

doi:10.3760/j.issn.1673-4777.2024.12.005

Abstract：Objective To explore the mechanism of 5-fluorouracil(5-FU)combined with oxaliplatin(L-OHP)on cisplatin(DDP)resistance in non-small cell lung cancer through microRNA-92a(miR-92a)/Wnt/β-catenin pathway.Methods Cultivate human non-small cell lung cancer cells(A549)in vitro and construct the DDP resistance model.The experimental groups are as follows:A549 group was the normal A549 cells,A549/DDP group was the DDP resistant model cells,A549+DDP group was the A549 group co-cultured with DDP,A549/DDP+DDP group was the A549/DDP group co-cultured with DDP,A549/DDP+miR-92a inhibitor group was the A549/DDP group transfected with miR-92a inhibitor,5-FU+L-OHP group was the A549/DDP group co-cultured with 5-FU+L-OHP,5-FU+L-OHP+miR-92a mimics group was the 5-FU+L-OHP group transfected with miR-92a mimics,5-FU+L-OHP+miR-92a mimics+Wnt/β-catenin inhibitor group was the 5-FU+L-OHP+miR-92a mimics group transfected with Wnt/β-catenin inhibitor.5-Ethynyl-2'-deoxyuridine experiment was used to detect cell proliferation rate,wounding healing assay was used to detect cell migration rate,Transwell experiment was used to detect cell invasion ability,fluorescence in situ hybridization was used to detect the expression of miR-92a;quantitative real-time polymerase chain reaction was used to detect the expression of miR-92a,Wnt4,and β-catenin;Western Blot was used to detect protein expression of Wnt4,β-catenin and CD44.Results Compared with A549 group,the expression level of miR-92a in A549/DDP group was significantly increased(P＜0.05).Compared with A549/DDP group,the migration rate and cells invasion number in A549/DDP+miR-92a inhibitor group were significantly reduced(both P＜0.05).Compared with A549/DDP group,the cell proliferation rate,cell invasion number and expression levels of miR-92a,Wnt4,β-catenin,and CD44 proteins in 5-FU+L-OHP group were significantly reduced(all P＜0.05).Compared with 5-FU+L-OHP group,5-FU+L-OHP+miR-92a mimics group showed a significant increase(all P＜0.05).Compared with 5-FU+L-OHP+miR-92a mimics group,5-FU+L-OHP+miR-92a mimics+Wnt/β-catenin inhibitor group showed a significant decrease[miR-92a:(0.49±0.07)vs(0.97±0.14),Wnt4:(0.37±0.05)vs(1.19±0.16),β-catenin:(0.27±0.04)vs(1.54±0.20)](all P＜0.05).Conclusion The combination of 5-FU and L-OHP can effectively improve the DDP resistance of A549 cells,inhibit cell proliferation and invasion,which may be related to downregulating the expression of proteins related to the miR-92a/Wnt/β-catenin signaling pathway.