5-fluorouracil inhibits the myeloid-derived suppressor cells and reduces their immunosuppressive ac-tivities in mice with liver cancer
10.3760/cma.j.issn.0254-5101.2014.09.001
- VernacularTitle:5-氟尿嘧啶对肝癌小鼠髓系抑制性细胞表达及功能的影响
- Author:
Liling XIA
;
Sulian ZHAO
;
Qin WEI
;
Xiaoqin XU
- Publication Type:Journal Article
- Keywords:
Orthotopic hepatocellular carcinoma;
5-fluorouracil;
Myeloid-derived suppressor cells;
T cell proliferation;
Interferon-γ
- From:
Chinese Journal of Microbiology and Immunology
2014;(9):651-656
- CountryChina
- Language:Chinese
-
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 (P<0.05).The highest proportions of MDSCs were observed in PBS treated group , followed by 10 mg/kg of 5-FU treated group , 30 mg/kg of 5-FU treated group and 50 mg/kg of 5-FU treated group .Ex-cept for comparing between PBS treated group and 10 mg/kg of 5-FU treated group, there were significant differences with the proportions of MDSCs in liver tissues among other groups (P<0.05).The levels of Arg-I and the activities of NOS in mice with liver cancer were higher than those in control group (P<0.05).The mice in PBS treated group showed the highest level of Arg-I and the strongest activities of NOS that were de-creased as concentrations of 5-FU increased( P<0.05).The levels of IFN-γin serum samples from mice with liver cancer were lower than those in control group , and the lowest level was detected in PBS treated group.IFN-γlevels were increased as concentrations of 5-FU elevated.Except for comparing between PBS treated group and 10 mg/kg of 5-FU treated group , significant differences with the levels of IFN-γin serum samples (P<0.05) were observed among other groups .No significant differences with the proliferation of T cells were observed among all groups after 24 hours of culture (P>0.05),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 .
