组蛋白去乙酰化酶抑制剂LBH589对多发性骨髓瘤细胞MM1R的抑制作用

本研究探讨新一代组蛋白去乙酰化酶抑制剂LBH589单药或者联合蛋白酶体抑制剂硼替佐米,对多发性骨髓瘤(MM)细胞的抗瘤效应。采用MTT法检测LBH589(10、20、50 nmol/L)及50 nmol/L分别联合硼替佐米(10、20 nmol/L)作用于人多发性骨髓瘤MM1R细胞24,48 h后的细胞增殖抑制作用;采用流式细胞术检测LBH589对MM1R细胞周期和细胞凋亡的影响;采用Western blot分析LBH589(10、20、50 nmol/L)作用MM1R细胞24 h后组蛋白H4乙酰化的程度。结果表明,LBH589单药及与硼替佐米联合均能够抑制MM1R细胞增殖,并与药物浓度和作用时间呈正相关。MM1R细胞经药物作用48 h后,G0/G1期细胞逐渐增多,G2/M期及S期细胞逐渐减少,细胞阻滞在G0/G1期,同时可见MM1R细胞的凋亡率增加,作用呈浓度依赖性,且LBH589与硼替佐米联合作用均较单药作用更加明显(均P<0.001);Western blot分析显示,不同浓度LBH589作用MM1R细胞24 h后组蛋白H4乙酰化的程度上调,呈浓度依赖性。结论:LBH589能够抑制MM1R细胞增殖,阻滞细胞周期,诱导细胞凋亡,且与硼替佐米联合对骨髓瘤细胞有协同作用。

Inhibitory Effect of Histone Deacetylase Inhibitor LBH589 on Multiple Myeloma MM1R Cells In Vitro

This study was purposed to explore the effect of a new generation of histone deacetylase inhibitor LBH589 alone or combined with bortezomib（Bor） on multiple myeloma cells（MM1R） in vitro.The effect of LBH589（10,20,50 nmol/L） alone or combined with Bor（10,20 nmol/L） on MM1R proliferation was detected by MTT method;the effect of LBH589 on cell cycle and apoptosis of MM1R cells were determined by flow cytometry;the histone H4 acetylation level of MM1R cells treated with LBH589（10,20,50 nmol/L） for 24 h was analyzed by Western blot.The results showed that the LBH589 alone or combined with Bor all could inhibit the proliferation of MM1R cells in a concentration-and time-dependent manner.After MM1R cells were treated with drugs for 48 h,the cells in G0/G1 phase increased,the cells in G2/M and S phase decreased,suggesting the arrest of cells in G0/G1 phase,at the same time,the apoptosis rate of MM1R cells treated with drugs increased in a concentration-dependent manner,while the effect of LBH589 combined with Bor was more obvious than that of LBH589 alone（P 0.001）.Western blot analysis showed that the histone H4 acetylation level was enhanced in concentration-dependent manner after MM1R cells were treated with different concentrations of LBH589 for 24 h.It is concluded that the LBH589 can inhibit the proliferation of MM1R cells,block the cell cycle,induce cell apoptosis,moreover LBH589 combined with Bor has synergistic effect on MM1R cells.