Expression of immune regulatory factors, chemokines and growth factors in differentiated gastric cancer cells treated with an anticancer bioactive peptide combined with oxaliplatin

用抗癌生物活性肽联合奥沙利铂治疗分化型胃癌细胞后,免疫调节因子、趋化因子和生长因子的表达

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Abstract

Gastric cancer is one of the most common malignant tumors of the digestive system. An anticancer bioactive peptide (ACBP) was previously shown to have an important role in inhibiting the differentiation of the MKN-45, N87 and GES-1 cell lines. However, to date, research on the effects of inflammatory factors in MKN-45, N87 and GES-1 cell lines after treatment with ACBP combined with oxaliplatin (OXA) has not been performed. To investigate the expression of immune regulatory factors, tumor growth factors and chemotactic factors in differentiated gastric cancer cells treated with ACBP combined with OXA, the expression of cytokines, including interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, basic fibroblast growth factor (bFGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, monocyte chemoattractant protein (MCP)-1, IFN-γ-induced protein-10, macrophage inflammatory protein (MIP)-1α, platelet-derived growth factor (PDGF)-BB, MIP-1β, regulated upon activation, normal T cell expressed and presumably secreted, TNF-α and VEGF, was assessed with cell experiments using the Bio-Plex ProT Human Cytokine 27-plex Assay. The results indicated that immune regulatory factor, tumor growth factor and chemotactic factor expression levels were different after treatment with ACBP alone or ACBP combined with OXA. IFN-γ, IL-1β, IL-17, IL-9, IL-10, IL-15, bFGF, GM-CSF and PDGF-BB expression was decreased in MKN-45 and N87 cells after ACBP treatment (P<0.01) and ACBP+OXA treatment (P<0.01) compared with the control cells, which indicated that ACBP inhibited tumor growth by regulating these cytokines, and the combination treatment inhibited tumor growth by regulating these cytokines. MIP-1β, MCP-1 and IL-13 expression was decreased in MKN-45 and N87 cells after the combination treatment compared with ACBP treatment alone, which indicated that ACBP combined with OXA was able to inhibit tumor growth by regulating these cytokines, while the mechanism of action of the ACBP and OXA is actually different, e.g. for OXA, this would be to cause DNA damage response. Therefore, the ACBP and OXA combination treatment may be closely associated with tumor progression and metastasis with immunological competence by MCP-1, MIP-1β and IL-13 expression.

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