摘要
目的探讨单用LBH589或联合硼替佐米及地塞米松对多发性骨髓瘤复发、难治患者骨髓单个核细胞的作用。方法采用四甲基偶氮唑蓝(MTT)法,检测LBH589(15、25、50)nmol/L及50 nmol/L分别联合硼替佐米(15、25)nmol/L及地塞米松(5、10)μmol/L对MM复发、难治患者骨髓单个核细胞作用24,48 h后的细胞增殖影响;采用流式细胞术测定LBH589对MM复发、难治患者骨髓单个核细胞细胞周期及细胞凋亡的影响;用Westernblot测定LBH589(15、25、50 nmol/L)对复发、难治患者骨髓单个核细胞作用24 h后组蛋白H4乙酰化的变化程度。结果单用LBH589或联合硼替佐米及地塞米松均能够使复发、难治患者骨髓单个核细胞增殖受到抑制,且与药物剂量和时间变化呈正比例。药物作用于MM复发、难治患者骨髓单个核细胞48 h后,G0/G1期细胞逐渐增加,G2/M期及S期细胞则逐渐降低,细胞在G0/G1期发生阻滞,可观察到细胞凋亡现象,且凋亡程度与药物剂量变化呈正比例,三药联合作用均较单药作用更加显著(P均<0.01);Westernblot测定显示,不同浓度LBH589对MM复发、难治患者骨髓单个核细胞作用24 h后组蛋白H4乙酰化的程度上调,且与药物剂量变化呈正比例。结论 LBH589能够使MM复发、难治患者骨髓单个核细胞增殖受到抑制,阻滞细胞周期,促进细胞凋亡,且三药联合对MM复发、难治患者骨髓单个核细胞有加强抗瘤细胞作用。
Objective To investigate the effect of LBH589 alone or combined with bortezomib and dexamethasone on bone marrow mononuclear cells of patients with relapsed or refractory multiple myeloma. Methods Methyl thiazolyl tetrazolium （MYY）was used to detect the effect of LBH589（ 15,25,50） nmol/L and 50nmol/L respectively combined with bortezomib（ 15, 25 ） nmol/L and dexamethasone（5,10）mol/L on cell proliferation of bone marrow mononuclear cells of patients with relapsed or refractory multiple myeloma 24 h and 48 h later;flow cytometry was used to detect the effect of LBH589 on cell cycle and apoptosis of bone marrow mononuclear cells of patients with relapsed or refractory multiple myeloma;Westernblot was used to detect the effect of LBH589 （ 15,25,50 nmol/L）on the changes of degree of historic H4 acetylation of bone marrow mononuclear cells of patients with relapsed or refractory muhiple myeloma 24 h iater. Results LBH589 alone or combined with bortezomib and dexamethasone were able to inhibit proliferation of bone marrow mononuclear cells of patients with relapsed or refractory multiple myeloma,and its relationship with drug dose and time was direct ratio. 48 h after bone marrow mononuclear cells of patients with relapsed or refractory multiple myeloma treated with drugs, G0/G1 phase ceils gradually increased, G2/M phase and S phase ceils gradually decreased, G0/G1 phase occurred cell block, cell apoptosis was observed, and apoptosis degree was positively proportional with drug dose ,combined effect of the 3 drugs was more significant than any single drug（ P all 〈 0.01 ） ;Westemblot showed that degree of histone H4 aeetylation increased 24 h after different concentrations of LBH589 on bone marrow mononuclear cells of patients with relapsed or refractory multiple myeloma,and it was positively proportional with drug dose. Conclusion LBH589 can inhibit proliferation of bone marrow mononuclear cells of patients with relapsed or refractory multiple myeloma, arrest cell cycle, promote apoptosis,and the combination of 3 drugs can strengthen the anti-tumor effects of ceils.
出处
《实用癌症杂志》
2016年第3期407-410,共4页
The Practical Journal of Cancer
关键词
LBH589
MM复发
难治患者骨髓单个核细胞
组蛋白乙酰化
LBH589
Bone marrow mononuclear cells of patients with relapsed or refractory multiple myeloma
Histone aeetylation
