帕比司他影响黑色素瘤生长和免疫原性机制的实验研究OA北大核心

Objective:To investigate the effects of the histone deacetylase(HDAC)inhibitor panobinostat on melanoma growth,tumor immunity,and the underlying mechanisms.Methods:B16F0 melanoma cells were cultured and treated with different concentrations of panobinostat.The effect of panobinostat on HDAC expression in B16F0 cells was detected by WB.The effects of panobinostat on the proliferation,migration,invasion,apoptosis and cell cycle of B16F0 cells were detected by CCK-8 assay,wound-healing assay,Transwell assay and flow cytometry,respectively.The effect of panobinostat on gene expression in B16F0 cells was detected using transcriptome analysis and verified by qPCR.Flow cytometry was used to detect the effect of panobinostat on the expression of MHCⅠ/Ⅱ in B16F0 cells.B16F0 cells and bone marrow-derived dendritic cells(BMDC)were co-cultured to assess the effects of panobinostat on the expression of CD11c,CD80 and CD86 in BMDC cells.A xenograft mouse model was used to evaluate the effects of panobinostat on tumor growth and host immune function.Results:panobinostat promoted the acetylation of H3 and α-tubulin proteins in B16F0 cells(P<0.01 or P<0.001 or P<0.000 1),inhibited cell proliferation,migration,and invasion,promoted apoptosis,and induced G1-phase cell cycle arrest(P<0.05 or P<0.001 or P<0.000 1).Additionally,panobinostat enhanced surface expression of MHC Ⅰ/Ⅱ on B16F0 cells and promoted BMDC maturation(all P<0.01).Transcriptomic analysis showed that panobinostat upregulated the expression of E-cadherin and antigen presentation related genes in B16F0 cells,and inhibited the expression of N-cadherin,vimentin,c-Myc and CDK1,which was confirmed by qPCR.In vivo,panobinostat suppressed xenograft tumor growth and enhanced immune function in tumor-bearing nude mice(P<0.05,P<0.000 1).Conclusion:panobinostat can inhibit the malignant biological behavior of B16F0 cells,promote apoptosis,regulate tumor immunity,and enhance immune function of tumor-bearing nude mice.