[Neutrophil extracellular traps promote the proliferation, invasion and migration of prostate cancer cells by upregulating IL-8 expression in DU145 human prostate cancer cells].

Abstract

Objective To investigate the effects of neutrophil extracellular traps (NETs) on proliferation, migration, and invasion of human prostate cancer and its related mechanisms. Methods The expressions of interleukin-8 (IL-8), lymphocyte antigen 6G (LY6G) and citrullinated histone H3 (H3CIT) in 28 cases of tumor tissues and adjacent tissues were detected by immunohistochemical staining. Neutrophils were extracted from the patients and stimulated with PMA to form NETs in vitro. The up-regulated genes of DU145 cells stimulated by NETs were detected by RNA-seq, and verified by real time quantitative PCR and Western blot analysis. KEGG and GO analyses of upregulated genes were performed using the DAVID database. The proliferation, invasion and migration ability of DU145 cells was assessed by CCK-8 assay, Transwell^TM and scratch assay. After knockdown of IL-8 expression in DU145 cells, the changes of proliferation, invasion and migration ability of DU145 cells were tested over again. Results The expression levels of IL-8, LY6G, and H3CIT in tumor sites were significantly higher than those in adjacent tissues. After co-incubated with NETs, the expression of 638 genes including IL-8 were up-regulated in DU145 cells, which related to phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway, cell proliferation and invasion. NETs can promote the proliferation, invasion and migration of DU145. After silencing IL-8, the ability of NETs to promote the proliferation, invasion and migration of DU145 was decreased. Conclusion NETs promote proliferation, migration, and invasion of DU145 by upregulating the expression of IL-8 in DU145 cells.