[摘 要] 目的：探究组蛋白去乙酰化酶（HDAC）抑制剂帕比司他对黑色素瘤生长和免疫性的影响及其机制。方法：常规培养 黑色素瘤细胞B16F0，用不同浓度的帕比司他处理细胞，WB法检测帕比司他对B16F0细胞中HDAC表达的影响，CCK-8法、划痕 愈合实验、Transwell实验和流式细胞术分别检测帕比司他对B16F0细胞增殖、迁移和侵袭能力，以及细胞凋亡和周期的影响。转 录组学检测帕比司他对B16F0细胞基因表达的影响，用qPCR法加以验证。流式细胞术检测帕比司他对B16F0细胞表面MHC Ⅰ/Ⅱ类 分子表达的影响，B16F0与骨髓来源树突状细胞（BMDC）共培养检测帕比司他对BMDC细胞表达CD11c、CD80和CD86的影响， B16F0细胞移植瘤实验检测帕比司他对移植瘤生长和裸鼠免疫功能的影响。结果：帕比司他促进B16F0细胞中组蛋白3（H3）和 α-微管蛋白（α-TUB）蛋白乙酰化（P < 0.01或P < 0.001或P < 0.000 1），抑制B16F0细胞增殖、迁移和侵袭能力，促进其凋亡，并使 细胞周期阻滞于G1期（P < 0.05或P < 0.001或P < 0.000 1），促进B16F0细胞表面表达MHC Ⅰ/Ⅱ类分子表达并促进共培养BMDC 成熟（均P < 0.01）。转录组学检测结果显示，帕比司他促进B16F0细胞中E-cadherin和抗原提呈相关基因的表达，抑制N cadherin、vimentin、c-Myc和CDK1的表达，qPCR法验证了这些结果。帕比司他抑制裸鼠移植瘤的生长并增强荷瘤裸鼠的免疫功 能（P < 0.05, P < 0.000 1）。结论：帕比司他可抑制B16F0细胞的恶性生物学行为，促进其凋亡，调控其免疫性，增强荷瘤裸鼠的 免疫功能。

[Abstract] 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 MHC Ⅰ/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.

[基金项目] 四川省医学会项目（No. S22013）；南充市市校合作项目（No. 22SXQT0311）；川北医学院校级科研发展基金项 目（No. CBY23-ZDA07）