METHODS: HDAC8 expression was analyzed in The Cancer Genome Atlas (TCGA)-pan-cancer dataset. The expression of HDAC8 in osteosarcoma cell lines was detected by western blot. TM-2-51, an activator of HDAC8, was taken to promote HDAC8 expression in osteosarcoma cells. Cell Counting Kit-8 (CCK-8) assay was applied to analyze cell viability changes and colony formation while 5-ethynyl-29-deoxyuridine (EdU) assays were used to evaluate cell proliferation. The migration and invasion abilities were analyzed by transwell assay, the distributions of cell cycle were analyzed by flow cytometry, and xenograft models were used to study the effect of HDAC8 activation in vivo. Furthermore, the mechanism underlying HDAC8\'s influence in osteosarcoma was analyzed by western blot assay.
RESULTS: Our study demonstrated that activation of HDAC8 in osteosarcoma cells can suppress cell viability, proliferation, migration, invasion, and arrest cell cycle of the osteosarcoma cells via TP53 and STAT3/ERK signaling pathway. Xenograft models confirmed that HDAC8 activation can reduce tumor growth in vivo.
CONCLUSIONS: The activation of HDCA8 could contribute negatively to osteosarcoma proliferation, and HDAC8 may represent a valuable therapeutic target in osteosarcoma therapy.
方法:在癌症基因组图谱(TCGA)-泛癌症数据集中分析HDAC8表达。Westernblot检测HDAC8在骨肉瘤细胞系中的表达。采取HDAC8的激活剂TM-2-51促进骨肉瘤细胞中HDAC8的表达。细胞计数试剂盒-8(CCK-8)测定用于分析细胞活力变化和集落形成,而5-乙炔基-29-脱氧尿苷(EdU)测定用于评估细胞增殖。通过transwell实验分析迁移和侵袭能力,通过流式细胞术分析细胞周期的分布,和异种移植模型用于研究HDAC8活化在体内的作用。此外,通过westernblot分析HDAC8对骨肉瘤影响的潜在机制。
结果:我们的研究表明,骨肉瘤细胞中HDAC8的激活可以抑制细胞活力,扩散,迁移,入侵,并通过TP53和STAT3/ERK信号通路阻滞骨肉瘤细胞的细胞周期。异种移植模型证实HDAC8活化可降低体内肿瘤生长。
结论:HDCA8的激活对骨肉瘤的增殖有负向作用,HDAC8可能是骨肉瘤治疗中一个有价值的治疗靶点。