Suberoylanilide hydroxamic acid inhibits proliferation and promotes apoptosis of mouse myeloma Sp 2 / 0 cells through activating p 53 / caspase-3 signaling
Suberoylanilide hydroxamic acid inhibits proliferation and promotes apoptosis of mouse myeloma Sp 2 / 0 cells through activating p 53 / caspase-3 signaling
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发表时间：
2018
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通讯作者：
Yanliang Bai;L. Huo;Chenyu Zhang;M. Shi;Na Fang;S. Ji;K. Sun
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作者：
Yanliang Bai;L. Huo;Chenyu Zhang;M. Shi;Na Fang;S. Ji;K. Sun
多发性骨髓瘤（MM）被认为是世界上癌症相关死亡的最大贡献者之一。辛二酰苯胺异羟肟酸（SAHA）是一种组蛋白去乙酰化酶抑制剂，广泛用于治疗癌症。然而，SAHA在MM中的作用及其潜在机制仍然难以捉摸。本研究采用CCK-8法检测小鼠骨髓瘤Sp2/0细胞活力。用5-乙炔基-20-脱氧尿苷和集落形成试验检测小鼠骨髓瘤Sp20细胞的增殖。流式细胞仪检测细胞凋亡，Annexin V-APC/7-AAD凋亡试剂盒检测细胞凋亡。Western blot检测PCNA、Bax、p53、cleaved caspase-8、cleaved caspase-9、cleaved caspase-3和cleaved PARP蛋白水平。SAHA以剂量和时间依赖的方式降低小鼠骨髓瘤Sp2/0细胞的存活率。此外，SAHA抑制小鼠骨髓瘤Sp2/0细胞的增殖，涉及EdU阳性细胞的数量减少和集落形成能力降低。SAHA还能促进小鼠骨髓瘤Sp2/0细胞凋亡，表现为PCNA水平降低和Bax水平升高。此外，SAHA激活了p53/Caspase-3信号通路，伴随着p53、切割的caspase-8、切割的caspase-9、切割的caspase-3和PARP蛋白的上调。综上所述，这些结果表明，SAHA通过激活p53/Caspase-3信号通路抑制小鼠骨髓瘤Sp2/0细胞的增殖并促进其凋亡。
Multiple myeloma (MM) is considered as one of the largest contributors to cancer-related deaths in the world. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, is used extensively for treating cancers. However, the effect of SAHA and its underlying mechanisms in MM remain elusive. In this study, the viability of mouse myeloma Sp2/0 cells was assessed by CCK-8 assay. Proliferation of mouse myeloma Sp2/0 cells was evaluated by 5-ethynyl-20-deoxyuridine and colony formation assay. Apoptosis was determined by flow cytometry using Annexin V-APC/7-AAD apoptosis kit. Western blot was carried out to detect protein levels of PCNA, Bax, p53, cleaved caspase-8, cleaved caspase-9, cleaved caspase-3 and cleaved PARP. SAHA decreased the viability of mouse myeloma Sp2/0 cells in a doseand a time-dependent manner. Furthermore, SAHA repressed proliferation of mouse myeloma Sp2/0 cells involving a decreased number of EdU positive cells and a reduced colony-forming ability. Furthermore, SAHA promoted apoptosis of mouse myeloma Sp2/0 cells, as evidenced by the decreased level of PCNA and the increased level of Bax. Moreover, SAHA activated the p53/Caspase-3 signaling pathway, accompanying with upregulation of p53, cleaved caspase-8, cleaved caspase-9, cleaved caspase-3 and PARP protein. Taken together, these findings suggest that SAHA inhibits proliferation and promotes apoptosis of mouse myeloma Sp2/0 cells through activating the p53/Caspase-3 signaling pathway.