The Study Of The Anti-Tumor Mechanism Of Astragalus Polysaccharide In B16-F10Tumor Bearing Mice Based On Myeloid-derived Suppressor Cells

Astragalus is the root of membranaceus astragalus andmongholicus astragalus which are perennial leguminous herbs.Astragalus Polysaccharide is the main biological active component ofAstragalus, which has effects of anti-cancer, lowering blood sugar,lowering blood pressure, immune regulation, anti-inflammatory,antiviral, antioxidant, hepatoprotective and so on. Currently,Astragalus Polysaccharide has been widely used in clinical treatments.Tumor immune escape is one of the reasons why there aren'tbetter effects of tumor treatment. Myeloid-derived suppressor cells(MDSC) are heterogeneous cells whose surface marker isGr-1~+CD11b~+, and they're one of the most important cells to causeimmune escape. It has been a new direction that reducing tumorimmune escape by inhibiting the generation of MDSC. At present, theanti-tumor immune mechanisms of Astragalus polysaccharide hasinvolved effects on some cells which are T cells, B cells, natural killer cells and so on, but there don't have enough studies about the effectson MDSC. This thesis chose B16-F10tumor bearing mice to be thesubject investigated, in order to investigate the effects and molecularmechanism on anti-immune tolerance of Astragalus Polysaccharide inB16-F10tumor bearing mice based on Myeloid-derived suppressorcells. This paper as well as wanted to provide evidences for theanti-tumor immune mechanisms of Astragalus polysaccharide. Themain work as follow:1. Mice were subcutaneously implanted with B16-F10tumor cells inthe right back region. The role of Astragalus polysaccharide on thein vivo antitumor activity was determined by the tumor volumeand the tumor inhibitory rate in B16-F10tumor bearing mice. Theeffects of Astragalus polysaccharide on MDSC in B16-F10tumorbearing mice was determined by flow cytometry (FCM). Themolecular mechanism on anti-immune tolerance of AstragalusPolysaccharide in B16-F10tumor bearing mice based onMyeloid-derived suppressor cells was investigated by theproportion of CD4~+CD25~+Foxp3~+regulatory T cells and thesecretion level of IL-10, TGF-β, VEGF, IFN-γ and TNF-α. Theresult displayed that the tumor inhibitory rate of CTX group,Astragalus polysaccharide of low dose group, Astragaluspolysaccharide of low dose+CTX group, Astragalus polysaccharide of high dose group, and Astragalus polysaccharideof high dose+CTX group was respectively53.82%,35.26%,71.42%,49.82%, and78.89%. Compared with untreated group, thetumor volume of Astragalus polysaccharide of low dose group,Astragalus polysaccharide of low dose+CTXgroup, Astragaluspolysaccharide of high dose group, and Astragalus polysaccharideof high dose+CTX group was decreased significantly on sixth dayP<0.01. Compared with CTX group, the tumor volume ofAstragalus polysaccharide of low dose+CTX group and Astragaluspolysaccharide of high dose+CTX group was decreasedsignificantly on the sixth day, eighth day, tenth day, and twelfthday P<0.01. Compared with untreated group, the proportion ofMDSC of CTX group, Astragalus polysaccharide of low dosegroup, Astragalus polysaccharide of low dose+CTX group,Astragalus polysaccharide of high dose group, and Astragaluspolysaccharide of high dose+CTX group was decreased P<0.01,as well as the proportion of CD4~+CD25~+Foxp3~+regulatory T cellsand the secretion level of IL-10, TGF-β, and VEGF of groups weredecreased significantly P<0.01, and the secretion levels ofTNF-α and IFN-γ were increased significantly P<0.05, P<0.01.2. Mice were subcutaneously implanted with B16-F10tumor cells inthe right back region. The role of Astragalus polysaccharide on synergist and attenuation was determined by the body weight,spleen index and biochemical indicators in B16-F10tumor bearingmice. Compared with normal group, the result displayed that thebody weight of CTX group was decreased P<0.05, but theredidn't have significantly difference in Astragalus polysaccharidetherapy group on sixth day. Compared with CTX group, the spleenindex of Astragalus polysaccharide of low dose group andAstragalus polysaccharide of high dose group was increasedsignificantly on the sixth and eighth day P<0.01, as well as theblood creatinine, the blood urea nitrogen, and the alaninetransaminase of Astragalus polysaccharide of low dose group,Astragalus polysaccharide of low dose+CTX group, Astragaluspolysaccharide of high dose group, and Astragalus polysaccharideof high dose+CTX group were decreased significantly P<0.05,P<0.01.