2-甲氧基雌二醇对原代骨髓瘤细胞分化的作用

Effect of 2-Methoxyestradiol on Differentiation of Primary Myeloma Cells

本研究观察2-甲氧基雌二醇对多发性骨髓瘤患者原代细胞诱导的分化作用。采用CD138+磁珠分离纯化7例骨髓瘤患者原代骨髓瘤细胞,通过形态观察、细胞表面标志分析和细胞分泌轻链蛋白的情况,观察2-甲氧基雌二醇对多发性骨髓瘤原代骨髓瘤细胞分化的影响。结果表明:患者原代骨髓瘤细胞经0.5μmol/L2-甲氧基雌二醇分别作用36及72小时后,细胞形态向成熟阶段发展,表现为细胞胞核缩小,胞浆丰富,核浆比例下降,核仁减少或消失,核染色质变粗、变密。CD49e阳性细胞率由(11.02±1.75)%(DMSO对照组)增加到(23.80±1.62)%(36小时组)及(35.68±1.85)%(72小时组),差异具有统计学意义(P<0.05);细胞分泌轻链蛋白由(225.7±30.4)ng/ml(DMSO对照组)升高到(296.7±18.8)ng/ml(36小时组)及(378.9±15.8)ng/ml(72小时组),差异具有统计学意义(P<0.05)。结论:较低浓度2-甲氧基雌二醇可诱导骨髓瘤患者原代骨髓瘤细胞向成熟阶段分化。

In order to investigate the differentiation-inducing effect of 2-methoxyestradiol （2ME2）, an estrogen derivative, on CD138^＋ （Syndecan-1） primary myeloma cells from 7 patients with myeloma, primary myeloma cells from 7 patients were enriched by using CD138 immunomagenetic beads. The enriched CD138^＋ （ Syndecan-1 ） myeloma cells treated with 0.5 μmol/L 2ME2 for 36h and 72 hours were used to observe the differentiation changes with expression of CD49e and to quantitatively detect the fight-chain secretion in the supernatants. The results indicated that 2ME2 caused morphological and immunophenotypic changes with light-chain secretion in the supernatant, and the typical features of differentiation of CD138 ^＋ （Syndecan-1） primary myeloma cells. CD138^＋ （Syndecan-1） myeloma cells became more and more mature in morphology, with decreased ratio of nucleus to plasma, disappearance of nucleoli, and pyknosis of chromatin . The result of detecting the expression of CD49e of CD138^＋ （ Syndecan-1 ） myeloma cells showed the obvious up-regulation of CD49e expression after exposure to 2ME2 for 72 hours. Quantitative assay for light chain secretion in the supernatant of bone marrow CD138^＋ cells from patients showed remarkable increment at 72 hours. It is concluded that lower concentrations of 2-methoxyestradiol can induce differentiation of bone marrow CD138^＋ cells from multiple myeloma patients.