5-fluorouracil inhibits the myeloid-derived suppressor cells and reduces their immunosuppressive ac-tivities in mice with liver cancer / 中华微生物学和免疫学杂志

ABSTRACT

Objective To investigate the effects of 5-fluorouracil (5-FU) on the distribution, pro-portion and immunosuppressive activities of myeloid-derived suppressor cells (MDSCs) in a mouse model of liver cancer.Methods Orthotopic transplantation of H22 cell line was performed to establish the mouse model of orthotopic liver cancer.Forty mice were randomly divided into four groups (n=10) on the 7th day after transplantation.Three different doses of 5-FU (10 mg/kg, 30 mg/kg and 50mg /kg) and 0.4 ml of PBS were respectively given to the mice in each group for 10 consecutive days .A control group without canc-er cell transplantation was set up correspondingly .The distribution of MDSCs in mice liver tissues was detec-ted by immunohistochemistry .The proportions of MDSCs in spleen tissues were tested by flow cytometry . The levels of IFN-γand Arginase-I ( Arg-I) in serum samples were analyzed by enzyme-linked immunosor-bent assay.The activities of nitric oxide synthetase (NOS) in serum samples were tested by chemical colori-metry.The proliferation of T lymphocytes was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltet-razolium bromide (MTT) test.Results 5-FU reduced the tumor size and alleviated the adhesion between liver tissues and abdominal cavity in mice with liver cancer in a dose-dependent manner .The proportions of MDSCs in liver and spleen tissues from mice in four model groups were significantly higher than those in con - trol group (P0.05),but that were decreased in model groups than those in control group after 48 hours of culture (P<0.05).T cells from mice in PBS treated group showed the lowest level of proliferation .T cell proliferation was enhanced upon the treatment of 5-FU in a dose-dependent manner .Except for comparing between PBS treated group and 10 mg/kg of 5-FU treated group, significant differences with T cell proliferation were observed among other groups (P<0.05).The proportions of MDSCs in liver and spleen tissues were positively correlated with the levels of Arg -I and the activities of NOS, but negatively correlated with IFN-γlevel and T cell proliferation at the time point of 48 h.Conclusion To a certain extent , 5-FU could reduce the numbers of MDSCs in liver and spleen tis-sues from mice with liver cancer , inhibit immunosuppressive activities of MDSCs and restrain the growth of the tumor in a dose-dependent manner .