中国组织工程研究2012，Vol.16Issue(6)：1062-1066,5.DOI:10.3969/j.issn.1673-8225.2012.06.025
组蛋白去乙酰化酶抑制剂SAHA诱导骨髓瘤细胞的凋亡
Novel histone deacetylase inhibitor SAHA induces the apoptosis of myeloma cells in vitro
于涛 1张鹏 1鹿全意 1刘银梅1
作者信息
- 1. 厦门大学附属中山医院血液科,福建省厦门市,361004
- 折叠
摘要
Abstract
BACKGROUND: SAHA is a new kind of histone deacetylase inhibitors (HDACI), the research about the effect of HDACI on myemola cells is rare, and the molecular mechanism of its induction of apoptosis is still poorly understood.OBJECTIVE: To investigate the effects of SAHA on proliferation and apoptosis of multiple myeloma cell line U266 cells in vitro and its possible mechanism.METHODS: The proliferation of U266 cells was measured by trypan blue exclusion method and colorimetric tetrazolium; the AlllexinV and PI staining was used to detect the apoptosis rates of U266 cells by flow cytometry, and the apoptotic morphological change was observed with Hoechst33342 staining; the expression of cell signaling proteins Ras/Raf /Mek /Erk were detected by Western-blot analysis.RESULTS AND CONCLUSION: The trypan blue exclusion method and colorimetric tetrazolium showed that SAHA could inhibit the proliferation rate of U266 cells and in a time-dose dependent manner. After treated with 0.5, 2 and 4 μmol/L SAHA for 48 hours, the apoptosis of U266 cells were (17.61±1.30)%, (41.13±3.80)% and (74.01±4.39)% respectively detected by flow cytometry, and in a dose dependent manner (P < 0.05). Distinct morphology changes between SAHA-treated group and control group were observed through fluorescence microscope by Hoechst 33342 staining; cell apoptosis such as karyopyknosis and nuclear fragmentation were significant in SAHA-treated group while in control group such changes were not obvious. The Western blot analysis showed that the phosphorylation of Raf-1 and its downstream ERK kinases were inhibited obviously after treated with SAHA and remarkable down-regulated when treated with the agent for 48 hours. SAHA can inhibit the proliferation of multiple myeloma cell line U266 cells and induce their apoptosis, the intercept of the signal pathway Ras/Raf /Mek /Erk is one of the underlying mechanism.关键词
组蛋白去乙酰化酶抑制剂/多发性骨髓瘤/SAHA/凋亡/细胞外调节蛋白激酶分类
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于涛,张鹏,鹿全意,刘银梅..组蛋白去乙酰化酶抑制剂SAHA诱导骨髓瘤细胞的凋亡[J].中国组织工程研究,2012,16(6):1062-1066,5.
