Anti-tumor and Phenotypic Regulation Effect of Matrine on Dendritic Cells through Regulating TLRs Pathway

Objective To investigate the effects of matrine on antigen presentation of dendritic cells(DCs),and to explore the pharmacological mechanism of matrine on anti-tumor effect.Methods Different concentrations(0,1,2,4,8 and 16µg/mL)of matrine were co-cultured with DCs,the harvested DCs were co-cultured with antigens of Lewis lung cancer(LLC)cells,and then DCs and T cells were co-cultured to produce DCs-activated killer(DAK)cells,which have significant tumor-killing activity.The expression of cytokines,mRNA and protein of toll-like receptors(TLRs)in DCs were detected by enzyme linked immunosobent assay,polymerase chain reaction and Western blot,respectively.And the killing effect of DAK were measured by MTT assay.Results Matrine significantly increased the mRNA expression of TLR7,TLR8,myeloid differentiation factor 88(MyD88),tumor necrosis factor receptor-associated factor 6(TRAF-6)and IκB kinase(IKK),as well as the protein expression of TLR7 and TLR8,and up-regulated the levels of interleukin-12(IL-12),IL-6 and tumor necrosis factor-α(TNF-α),meanwhile,it also increased the expressions of MHC-II,CD54,CD80 and CD86 in DCs.DCs-activated effector T cells had significant tumor-killing activity.When the concentration of matrine was more than 4µg/mL,all indices had significant difference(P<0.01 or P<0.05).Conclusion Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway,promoting the secretion of inflammatory cytokines and enhancing immune function.