| Objective: To investigate the effect of ulinastatin and Doxifluridine on microenvironment of tumor immune and tumor growth and cell apoptosis,and to investigate the regulatory function of UTI combined with DFD on immunosuppressive state.Methods: Establish tumor bearing BALB/c mice model with 4T1 cells.Seventy mice were randomly divided into seven groups: blank group,two drug single using groups(UTI and DFD)and four UTI combined with gradient does DFD groups.After group administration,the inhibition rate of tumor sizes was calculated.Flow cytometric dyeing was used to detect CD4+CD25+Foxp3+ Treg,CD11c+MHC?+ cells,CD11c+CD40+ cells and CD11c+CD86+ cells percentages,which were applied to the inguinal lymph nodes and.Tumor were dissected and the expression of interleukin-10 and transforming growth factor-? was 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,both drug single using groups and combination groups could significantly inhibit 4T1 tumor growth,decreased the rate of CD4+CD25+Foxp3+Treg/CD4+T cells,the expression of IL-10,TGF-? and CD34(P<0.001).The rate of CD11c+MHC?+ cells/CD11c+ cells,CD11c+CD40+ cells/CD11c+ cells and CD11c+CD86+ cells/CD11c+cells in both drug single using groups and combination groups was significantly increased.The apoptotic rates were higher determined by TUNEL in both drug single using groups and combination groups than those in blank group(P<0.001).UTI combined with 3mg DFD group have the most significant effects than drug single using groups.Conclusion: UTI combined with DFD can suppress the tumor growth in mice with normal immune function,UTI combined with 3mg DFD has most significant effect among the combination groups and reduced the dose of DFD.The mechanism may be related with regulating CD4+CD25+Foxp3+ Treg,CD11c+MHC?+ cells,CD11c+CD40+ cells and CD11c+CD86+ cells,IL-10 and TGF-? in the tumor microenvironment. |
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