Growth-inhibition of S180 residual-tumor by combination of cyclophosphamide and chitosan oligosaccharides in vivo

Chitosan oligosaccharides (COS), hydrolyzed products of chitosan, have recently been reported to have various biological activities. Herein, the present study was undertaken to assess the ability of COS to potentiate the antitumor effect of cyclophosphamide (CTX) as well as alleviating the CTX-associated toxicities in vivo, in a residual-tumor; a model which is closer to clinical surgery. Sarcoma 180 (S180) residual-tumor mice were divided into 6 groups (n = 6); including control, CTX, COS 40 mg/kg, COS 80 mg/kg, and combination groups (CTX + COS 40, CTX + COS 80). Animals were killed 18 days post-intraperitoneal administration and the tumors were weighed. The spleens were harvested to determine lymphocytes proliferation and NK cell activities; blood cells were evaluated by flow cytometry, and the expression levels of TNF-α were measured using ELISA. Notably, the combined therapy (CTX + COS80) showed the most effective reduction of the tumor weight, the highest inhibition of tumor growth, and proliferation, when compared with control as well single CTX group. Additionally, COS was able to recover the CTX-induced decreases in the lymphocyte proliferation, splenocyte NK cell activity, TNF-α concentration, and abnormal CD4+/CD8+ T lymphocyte subset. The increase in infiltrating T cells and macrophages best explain the immunostimulatory effect of COS. Results herein highlighted the therapeutic potential of COS as adjuvant treatment during tumor chemotherapy.