Abstract： Objective To investigate the influence of hypoxia-induced gastric cancer cell-derived exosomes(exo)on neutrophil extracellular traps(NETs)formation and gastric cancer cell growth.Methods Exosomes were ex-tracted from SGC-7901 and HGC cells cultured under normoxic and hypoxic conditions,labeled as N-SGC-7901 exo,N-HGC exo,H-SGC-7901 exo,and H-HGC exo.Neutrophils were divided into phosphate-buffered solution(PBS)group,N-SGC-7901 group,N-HGC group,H-SGC-7901 group,H-HGC group,N-SGC-7901 exo group,N-HGC exo group,H-SGC-7901 exo group,and H-HGC exo group.Sytox Green staining was used to detect NETs formation in each group.SGC-7901 cells were divided into PBS/culture medium(CM)group,N-SGC-7901 exo/CM group,H-SGC-7901 exo/CM group,and H-SGC-7901 exo/CM+DNase group.HGC cells were divided into PBS/CM group,N-HGC exo/CM group,H-HGC exo/CM group,and H-HGC exo+DNase/CM group.Cell pro-liferation was assessed using the CCK8 assay,and colony formation experiment was performed to evaluate the clonogenic capacity of each group.Results Compared to the PBS group,N-SGC-7901 group,H-SGC-7901 group,N-HGC group,and H-SGC group showed increased NETs formation in neutrophils,with H-SGC-7901 group higher than N-SGC-7901 group and H-SGC group higher than N-HGC group.Similarly,compared to the PBS group,N-SGC-7901 exo group,H-SGC-7901 exo group,N-HGC exo group,and H-SGC exo group exhibited enhanced NETs for-mation,with H-SGC-7901 exo group higher than N-SGC-7901 exo group and H-SGC exo group higher than N-HGC exo group.In SGC-7901 cells,compared to the PBS/CM group,N-SGC-7901 exo/CM group and H-SGC-7901 exo/CM group showed significantly increased cell proliferation and clonogenicity(P＜0.01),with H-SGC-7901 exo/CM group higher than N-SGC-7901 exo/CM group(P＜0.001).However,H-SGC-7901 exo/CM+DNase group exhibited significantly reduced proliferation and clonogenicity compared to H-SGC-7901 exo/CM group.In HGC cells,compared to the PBS/CM group,N-HGC exo/CM group and H-HGC exo/CM group displayed significantly in-creased cell proliferation and clonogenicity(P＜0.01),with H-HGC exo/CM group higher than N-HGC exo/CM group(P＜0.001).H-HGC exo/CM+DNase group showed significantly decreased proliferation and clonogenicity com-pared to H-HGC exo/CM group.Conclusion Under hypoxic conditions,gastric cancer cell-derived exosomes promote the formation of NETs,thereby enhancing the growth of gastric cancer cells.