三氧化二砷对多发性骨髓瘤骨髓基质细胞增殖及分泌细胞因子影响.docVIP

三氧化二砷对多发性骨髓瘤骨髓基质细胞增殖及分泌细胞因子影响 　 作者：谭竞，刘霆，朱焕玲，孟文彤，余江 【摘要】 为了探讨三氧化二砷（As2O3）对多发性骨髓瘤（MM）患者骨髓基质细胞（BMSC）增殖及其分泌白细胞介素-6（IL-6）和血管内皮细胞生长因子（VEGF）能力的影响，用体外培养MM患者骨髓的方法获得BMSC。BMSC和MM细胞株CZ-1单独或共同培养，给予不同浓度As2O3（1-20.0 μmol/L）处理，用MTT法检测细胞活性，用ELISA法检测IL-6、VEGF的分泌水平。 结果表明： As2O3对CZ-1细胞有生长抑制作用，48小时后细胞生长抑制50 %的浓度（IC50）为2.3 μmol/L，但对BMSC的生长无影响； MM患者BMSC高分泌IL-6、VEGF，经As2O3作用后BMSC分泌IL-6、VEGF降低，骨髓瘤细胞和BMSC相互作用导致的过量IL-6、VEGF分泌也可被As2O3抑制，其抑制程度与对照组相比有显著性差异（Plt;0.05）。 结论： As2O3不能抑制BMSC的生长，但可以抑制其分泌IL-6及VEGF。 【关键词】 多发性骨髓瘤 　　Effect of Arsenic Trioxide on Bone Marrow Stromal Cells of Patients with Multiple Myeloma 　　Abstract To explore the effect of arsenic trioxide（As2O3）on growth and secretion of interleukin-6（IL-6）and vascular endothelial growth factor（VEGF）of bone marrow stroma cells (BMSC) from the patients with multiple myeloma (MM). Specimens of bone marrow aspiration from MM patients were used to establish BMSC cultures.BMSC and human MM cell line CZ-1 were cultured together or alone in the absence or presence of As2O3 at various concentrations（1-20.0 μmol/L）.Cell growth inhibition was assessed by MTT assay，cytokines in the culture supernatants were measured with ELISA.The results showed that As2O3 had cytostatic effect on CZ-1 with fifty percent growth inhibition （IC50）for 48 hours at 2.3 μmol/L.As2O3 did not inhibit the growth of BMSC.High levels of IL-6 and VEGF have been found in the culture supernatants of BMSC from MM patients.Cytokine production of BMSC treated with As2O3 significantly decreased as compared with controls（Plt;0.05）.Excitingly，even the increased cytokine production triggered by adhesion of MM cell and BMSC was also inhibited by As2O3.It is concluded that As2O3 has no inhibitory effect on cell growth of BMSC，but inhibit the production of IL-6 and VEGF by BMSC. 　　Key word multiple myeloma; arsenic trioxide; bone marrow stromal cell; cytokine 多发性骨髓瘤（multiple myeloma，MM）目前仍不能被治愈，骨髓基质细胞（bone marrow stromal cells，BMSC）在MM的发病机制中起着重要作用，自分泌和旁分泌的细胞因子白细胞介素-6(IL-6)、血管内皮细胞生长因子（v