Effect of ulinastatin and docetaxel on immune microenvironment of breast cancer

Abstract:

Objective：To investigate the effect of ulinastatin（UTI） and docetaxel（DCT） on immunocyte，immune factors and matrixes in breast cancer immune microenvironment and the tumor growth. Methods：4T1 breast cancer cells were cultured and the BALB/c mice were purchased to establish BALB/c mice model bearing 4T1 cells. Thirty-two mice were randomly divided into four groups：control group，UTI group，DCT group and UTI + DCT group. The tumor size was measured and the inhibition rate was calculated. Line flow cytometric dyeing was used to detect CD4+CD25+Foxp3+Treg content. The expression of interleukin-2（IL-2），IL-6 and IL-10 was detected by ELISA. The expression of matrix metalloproteinases 9（MMP-9） and tissue inhibitor of metalloproteinase 1（TIMP1） was detected by Western blot. Results：Both UTI and DCT can inhibit tumor growth and inhibitory effect was the most significant when UTI combined with DCT（P=0.000）. The rate of CD4+CD25+Foxp3+Treg/CD4+T cells was decreased in UTI group，DCT group and UTI + DCT group than in control group（P=0.000）. The expression of IL-6，IL-10 and MMP-9 was significantly decreased and the expres－sion of IL-2 and TIMP1 was increased in UTI group，DCT group and UTI + DCT group than in control group（P=0.000，P=0.000）. Conclusion：UTI combined with DCT can suppress the tumor growth in mice with normal immune function. The mechanism may be related with regulating CD4+CD25+Foxp3+Treg，IL-2，IL-6，IL-10，MMP-9 and TIMP1 in the tumor microenvironment.