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Jing Xu,1,2 ShengXiang Lv,1,2 Wei Meng,3 Fang Zuo4 1Department of Gastroenterology, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, 222000, People’s Republic of China; 2Department of Gastroenterology, First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, Jiangsu Province 222000, People’s Republic of China; 3Department of Functional Examination, Jinan Central Hospital, Jinan, Shandong Province 250014, People’s Republic of China; 4Department of Gastroenterology, Jinan Central Hospital, Jinan, Shandong Province 250014, People’s Republic of ChinaCorrespondence: Fang ZuoDepartment of Gastroenterology, Jinan Central Hospital, Jinan, Shandong Province 250014, People’s Republic of ChinaTel +86 13370582853Email zzfangf@163.comIntroduction: Gastric cancer occurred in China and even the whole East Asia with high incidence. The objective of this study was to investigate the role of IL-17 in gastric cancer cells mediated by LCN2 binding to SLPI.Methods: The expression of LCN2 and SPLI in gastric cancer cells and transfection effects were confirmed by RT-qPCR analysis. The proliferation, clone formation ability, invasion, migration, apoptosis, and cell cycle of gastric cancer cells were in turn detected by CCK-8 assay, clone formation assay, transwell assay, wound healing assay, and flow cytometry analysis. The combination between LCN2 and SLPI was determined by co-immunoprecipitation assay. The expression of Caspase-3, Bcl-2, cyclinB1, cyclinD1, MMP9, and SLPI in gastric cancer cells was detected by Western blot analysis.Results: LCN2 and SPLI exhibited the highest levels in AGS cells, and thus AGS cells were selected for the next experiments. Down-regulation of LCN2 suppressed the proliferation and clone formation ability of AGS cells treated with IL-17. IL-17 promoted the invasion and migration of AGS cells, which was partially reversed by the down-regulation of LCN2. Down-regulation of LCN2 mediated by IL-17 promoted apoptosis and suppressed the cell cycle of AGS cells.Discussion: Down-regulation of LCN2 mediated by IL-17 suppressed the proliferation and suppressed the migration and invasion and cell cycle of gastric cancer cells by targeting SLPI.Keywords: lipocalin-2, LCN2, interleukin-17, IL-17, gastric cancer cells, SLPI