| Background:Alcohol is one of the most widely consumed beverages in the world.The relationship between alcohol and cancer has been widely studied,mainly focusing on carcinogenesis.However,the effect of alcohol on tumor immune microenvironment and its molecular mechanism are still unclear.Our previous research showed that Jianpi Huayu Formula can weaken the immunosuppressive function of myelogenous suppressor cells in vivo and in vitro,thus reshaping the tumor immunosuppressive microenvironment and inhibiting the growth of liver cancer.In this study,we discussed the effect of long-term ethanol intake on the growth of subcutaneous liver cancer and immune cells,especially myelogenous suppressor cells,and the effect of Jianpi Huayu Formula on the growth and immune status of hepatocellular carcinoma under long-term ethanol intake.Methods:1.Long-term ethanol intake reshapes tumor immune microenvironment by targeting medullary inhibitory cells(1)In vivo experiment:Balb/c male rats aged 4-5 weeks were randomly divided into two groups:control drinking water group,5%alcohol group,2%alcohol group and 20%alcohol group.Mice in the 2%,5%and 20%alcohol groups were given drinking water containing 2%(v/v),5%(v/v)and 20%(v/v)absolute ethanol day and night,while the control group drank ordinary drinking water day and night for 2 weeks.After 2 weeks,3 mice were killed in each group.At the same time,BALB/c mice subcutaneous hepatoma model was established using hepatoma cell H22.The mice were killed for 3 weeks.(2)In vitro experiment:CCK8 was used to detect the effect of different concentrations of ethanol aqueous solution on the proliferation of H22 cells.2.Jianpi Huayu Prescription alleviates liver injury induced by long-term ethanol intakeIn vivo experiment:Balb/c mice aged 4-5 weeks were randomly divided into 5 groups:control drinking water group,JHD group,alcohol group,alcohol+JHD group.Drink ordinary drinking water or 20%(v/v)ethanol water solution day and night for 2 weeks.Two weeks later,three mice were killed in each group,and the BALB/c mice subcutaneous liver cancer model was established by using hepatoma cell H22.On the fifth day after the establishment of the model,the mice were consecutively administered with traditional Chinese medicine,24.96g/kg/d,for 3 weeks.Results:1.Long-term ethanol intake reshapes tumor immune microenvironment by targeting medullary inhibitory cells(1)Long-term consumption of 5%ethanol can reduce the M-MDSCs and G-MDSCs in the peripheral blood of normal mice and increase the CD8+T cells in the spleen.(2)Long-term consumption of 20%ethanol can reduce the M-MDSCs and G-MDSCs in the spleen of normal mice,while 2%ethanol does not change the M-MDSCs and G-MDSCs in the peripheral blood and spleen of mice.(3)5%and 20%ethanol inhibited the growth of subcutaneous H22 hepatoma,while 2%ethanol could not significantly inhibit the growth of subcutaneous hepatoma.(5)5%(v/v)and 20%(v/v)ethanol reduced M-MDSCs and G-MDSCs in peripheral blood,spleen and tumor.(6)20%(v/v)ethanol increased CD4+T and CD8+T cells in spleen and tumor tissue.2.Jianpi Huayu Prescription alleviates liver injury induced by long-term ethanol intake(1)Jianpi Huayu Decoction could not enhance ethanol-mediated inhibition of subcutaneous H22 hepatoma.(2)Jianpi Huayu Prescription alleviates liver injury induced by high concentration of alcohol.Conclusions:Long-term intake of 5%(v/v)and 20%(v/v)ethanol at medium and high concentrations can reduce MDSCs and subtypes in peripheral blood,spleen and tumor tissue,increase CD8+T cells,reduce the expression of immunosuppressive mediators Argl and iNOS in tumor tissue,improve the immune status of tumor-bearing mice,and inhibit the growth of H22 subcutaneous liver cancer.Although Jianpi Huayu Formula can not further enhance the inhibition of subcutaneous H22 liver cancer mediated by ethanol intake,it can reduce the liver injury caused by high concentration of ethanol. |
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