LCN2 Mediated by IL-17 Affects the Proliferation, Migration, Invasion and Cell Cycle of Gastric Cancer Cells by Targeting SLPI

Cancer Manag Res. 2020 Dec 14:12:12841-12849. doi: 10.2147/CMAR.S278902. eCollection 2020.

Abstract

Introduction: 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: IL-17; LCN2; SLPI; gastric cancer cells; interleukin-17; lipocalin-2.

Grants and funding

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