Effect of ulinastatin combined with doxifluridine on immune microenvironment of breast cancer

CHENG Xi; YIN Guo-bing; LI Xia; DAI Meng; TAN Ling

Abstract：Objective:To investigate the effect of ulinastatin combined with doxifluridine on tumor growth and tumor microenvironment.Methods:Tumor-bearing BALB/c mice model was established with 4T1 cells.Seventy mice were randomly divided into 7 groups:blank group,2 monotherapy groups and 4 UTI combined with gradient dose of DFD groups.After administration,the inhibition rate of tumor sizes was calculated.Flow cytometric dyeing was used to detect percentages of CD4 + CD25 + Foxp3 + Treg,CD11 c + MHC Ⅱ + cells,CD11 c + CD40 + cells and CD11c+ CD86+ cells;the expressions of interleukin-10 and transforming growth factor-β were tested by Western blot;immunohistochemistry was used to detect the expression of CD34;the apoptotic rates were revealed by TUNEL labeling.Results:Compared with blank group,each administration group inhibited 4T1 tumor growth and decreased the ratio of CD4 + CD25 + Foxp3 + Treg/CD4 + T cells and the expressions of IL-10,TGF-β and CD34 (P＜0.001);the ratios of CD11c+ MHC Ⅱ + cells/CD11c+ cells,CD11c+ CD40+ cells/CD11c+ cells and CD11c + CD86 + cells/CD11c + cells in each administration group were increased;the apoptotic rates were higher as determined by TUNEL in each administration group (P ＜ 0.001).UTI combined with 3 mg DFD group had the most significant effects than single drug treatment groups.Conclusion:UTI combined with DFD can suppress the tumor growth in mice with normal immune function,and UTI combined with 3 mg DFD has the most significant effect among the administration groups.The mechanism may be related with regulating CD4 + CD25 + Foxp3 + Treg,CD11c+ MHC Ⅱ + cells,CD11c+ CD40+ cells and CD11c+ CD86+ cells,IL-10 and TGF-β in the tumor microenvironment.