丁酸钠对黑色素瘤荷瘤小鼠的作用及机制探究  

Inhibition of mouse B16 melanoma by Sodium butyrate correlated to tumor associated macrophages differentiation suppression

作　　者：王俊杰 熊芬[2] 牟韵竹[2] 付天强 WANG Jun-jie;XIONG Fen;MOU Yun-zhu;FU Tian-qiang(Department of Dermatology in Yilong People's Hospital,Yilong Sichuan 637600 China;Department of Dermatology in Affiliated Hospital of North Sichuan Medical College,Nanchong Sichuan,611000 China)

机构地区：[1]四川省仪陇县人民医院皮肤科,四川仪陇637600 [2]川北医学院附属医院皮肤科,四川南充637000

出　　处：《海南医学院学报》2020年第5期321-324,329,共5页Journal of Hainan Medical University

基　　金：四川省教育厅课题(14ZB0196)~~

摘　　要：目的:探讨表观遗传修饰抑制剂-小分子化合物丁酸钠对B16黑色素瘤的作用及其机制,为临床黑色素瘤的治疗提供新视角。方法观察丁酸钠在体内、外对黑色素瘤B16的作用效果,采用MTT法检测不同浓度丁酸钠体外处理后细胞的凋亡率;流式细胞术检测肿瘤相关巨噬细胞的浸润情况;western-blotting检测肿瘤相关巨噬细胞因子的表达。结果:一定浓度的丁酸钠能有效地在体内、外对鼠源B16黑色素瘤产生抑制效应;与对照组相比,1.0 g/kg组、2.0 g/kg组、3.0 g/kg组的巨噬细胞分化都受到不同程度的抑制,其中5.0 g/kg组抑制效应最明显,差异具有统计学意义(P<0.01),同时下调肿瘤相关巨噬细胞因子的表达。结论丁酸钠能通过抑制肿瘤相关巨噬细胞的分化、增殖及下调促瘤巨噬细胞因子而抑制体内、外鼠黑色素瘤的生长,有助于促进对临床黑色素瘤表观遗传治疗的研究。Objective:As amember of the histone deacetylase inhibitor(HDACi)family,Sodium butyrate(NaB)was found out that could be used as a differentiation inducer of much cancer cell.But its effects on tumor microenvironment cells are not well recognized.The objectiveof this research is to investigate the effect of NaB on B16 melanoma and analysis its correlationmechanism.Methods:We observed the effect of sodium butyrate on B16 melanoma in vivo and in vitro.MTT method was performed to detect cell apoptosis rate after treatment.Tumor associated macrophage infiltration condition was detected by flow cytometry.Western-blotting and immunohistochemical method were used to detect the expression of tumor associated macrophage cytokines.Results:A certain concentration of sodium butyrate could effectively inhibit B16 melanoma growth in vivo and in vitro.Compared with the control group,macrophage differentiation in the 1.0 g/kg group,2.0 g/kg group and 3.0 g/kg group group were all inhibited to varying degrees.The inhibitory effect was most significant in the 5.0 g/kg group,and the difference was statistically significant(P<0.01).At the same time we observed the relevant macrophage factors were down-regulated compared to the control.Conclusion:Sodium butyrate could effectively inhibit B16 melanoma growth through suppressing tumor associated macrophage proliferation and reduce relevant pro-tumor macrophage factors expression,which may help to promote the clinical study of melanoma epigenetic therapy.

关 键 词：黑色素瘤B16细胞 丁酸钠 肿瘤相关巨噬细胞 

分 类 号：R739.5[医药卫生—肿瘤]