Chitooligosaccharides and N-acetyl-D-glucosamine stimulate peripheral blood mononuclear cell-mediated antitumor immune responses.

Abstract

The aim of the present study was to evaluate the anticancer effects of chitooligosaccharides (COS) and N-acetyl-D-glucosamine (NAG), as well as to investigate the possible mechanisms involved. MTT assay and flow cytometry were used to evaluate the effect of various concentrations of COS and NAG on the proliferation and differentiation of peripheral blood mononuclear cells (PBMCs). In addition, sarcoma 180 cells were transplanted into mice to establish a tumor model. COS and NAG were administered by gavage of various doses. The tumor inhibition rate, thymus and spleen indexes, natural killer (NK) cell activity, and interleukin-2 (IL-2) and interferon-γ (IFN-γ) serum levels were detected. Vascular endothelial growth factor (VEGF) expression levels, an important marker of angiogenesis, were also detected. As shown by immunohistochemistry, VEGF mRNA expression was decreased following treatment with COS and NAG, indicating that COS and NAG have an inhibitory effect on the expression of VEGF. The results from this study indicate that COS administered at a dose of 100 mg/kg and NAG at a dose of 300 mg/kg or 500 mg/kg can not only promote the differentiation of PBMCs and the secretion of IL-2 and IFN-γ, but can also inhibit the expression of VEGF mRNA in sarcoma 180 tumors. Our results show that the antitumor and immunoregulatory effects of COS and NAG are dose-dependent. Furthermore, the antitumor effect is achieved by the improvement of immunoregulation indirectly.