Effects of Astragalus Polysaccharide on the Development and Immune Escape of Non-Hodgkin's Lymphoma by Regulating Programmed Death Molecule 1/Programmed Death Ligand 1 Signaling Pathway
Objective To observe the therapeutic effect and mechanism of astragalus polysaccharide on non-Hodgkin's lymphoma(NHL).Methods Three kinds of NHL cells,WSU-DLCL2,BJAB and SP53,were cultured and treated with different concentrations(0,5,10,50,100,200,400 μmol/L)of astragalus polysaccharide.The cell viability was detected by cell counting kit-8(CCK-8)method to screen the optimal concentration of astragalus polysaccharide and the cells sensitive to astragalus polysaccharide.WSU-DLCL2 cells were divided into control group,astragalus polysaccharide group,BMS-1[programmed death molecule 1(PD-1)/programmed death ligand 1(PD-L1)pathway inhibitor]group,astragalus polysaccharide+BMS-1 group.The colony formation,apoptosis,migration and invasion of each group were detected,and the protein expression of PD-1/PD-L1 signaling pathway was detected by Western Blot.After co-culture of WSU-DLCL2 cells and CD8+T cells,the percentage and apoptosis of CD8+T cells,and the levels of interferon(IFN)-γ and tumor necrosis factor(TNF)-α in the supernatant were detected.Results The follow-up experiments selected 200 μmol/L astragaloside to treat WSU-DLCL2 cells.Compared with the control group,the number of WSU-DLCL2 cell colony formation,the number of migrating WSU-DLCL2 cells,the number of invading WSU-DLCL2 cells,the apoptosis rate of CD8+T cells,and the protein expression levels of PD-1 and PD-L1 in WSU-DLCL2 cells were significantly decreased in the Astragali polysaccharide group,the BMS-1 group and the Astragali polysaccharide+BMS-1 group(P<0.05),and the apoptosis rate of WSU-DLCL2 cells,the proportion of CD8+T cells,and the levels of IFN-γ and TNF-α in the supernatant of co-culture system were significantly increased(P<0.05);compared with astragali polysaccharide group and BMS-1 group,the number of WSU-DLCL2 cell colony formation,migrating WSU-DLCL2 cells,invading WSU-DLCL2 cells,CD8+T-cell apoptosis rate,and protein expressions of PD-1,PD-L1 in WSU-DLCL2 cells were further decreased in astragali polysaccharide+BMS-1 group(P<0.05),and the rate of WSU-DLCL2 cell apoptosis,the proportion of CD8+T-cells,and the levels of IFN-γ,TNF-α in the supernatant of co-culture system were significantly further elevated(P<0.05).Conclusion Astragalus polysaccharide can inhibit NHL cell proliferation,migration and invasion,promote its apoptosis and reduce immune escape,and its mechanism may be related to the inhibition of PD-1/PD-L1 signaling pathway.
astragalus polysaccharidenon-Hodgkin's lymphomaimmune escapeprogrammed death molecule 1(PD-1)programmed death ligand 1(PD-L1)BJAB cellsSP53 cellsWSU-DLCL2 cells