2-甲氧基雌二醇对骨髓瘤细胞系CZ-1细胞诱导分化作用浅谈.docVIP

2-甲氧基雌二醇对骨髓瘤细胞系CZ-1细胞诱导分化作用浅谈 　 作者：侯健，熊红，高巍然，姜华 【摘要】 本研究观察2-甲氧基雌二醇（2ME2）对骨髓瘤细胞是否具有直接的诱导分化作用。以自行建立的、能分泌λ轻链蛋白的骨髓瘤细胞系CZ－1细胞为研究对象，通过瑞氏染色观察其形态变化，用流式细胞术分析2ME2作用后细胞表面标志CD49e的表达率，采用免疫比浊法测定培养上清液中λ轻链蛋白浓度。结果表明： CZ-1细胞经01-0.5 μmol/L 2ME2作用72小时后细胞形态向成熟发展，见核浆比例降低，核仁减少或消失，染色质变得更粗糙更致密；细胞表面标志CD49e表达率明显上调，并呈浓度依赖性，与对照组比较统计学意义明显；0.1和0.5 μmol/L 2ME2处理72小时后，CZ-1细胞分泌λ轻链蛋白分别由29.3±2.77 μg/ml增至35.97±2.6 μg/ml（Plt;005）和增至79.67±1.88 μg/ml（Plt;0.01），显示浓度效应依赖关系。结论：较低浓度2ME2能促使CZ－1细胞向成熟阶段分化，2ME2这一作用的发现能为骨髓瘤的治疗提供新的有效的方法。 【关键词】 骨髓瘤 Multiple myeloma (MM) is generally regarded as incurable malignancy of plasma cells，which are terminally differentiated cells of B cell lineage［1］. Up to now chemotherapy and stem cell transplantation have still been the most important therapies and improved some MM patients prognosis to a certain extent. It is well known that this disease mainly occurred in the el-der. Since many old patients have little chance to accept transplantation and could not endure high-dose chemotherapy because of the poor visceral function or age，it is of very important significance to explore novel，effective and safe therapy. 2-Methoxyestradiol (2ME2)，once considered as an inactive end-metabolite of estradiol，has recently emerged as a very promising agent for cancer treatment［2］. Previous studies showed that it has a cytotoxic effect on various proliferating cells in vitro［3-5］. Despite being a natural derivative of estradiol (E2)， 　　2ME2 binds poorly to the estrogen receptors (ERs)，therefore its antiproliferative effects are not mediated by ERs［6］. Using xenografts and metastatic disease models in mice，it has been suggested that 2ME2 targets both the tumor cell and endothelial cell compartments by inducing apoptosis in rapidly proliferating cells and inhibiting blood vessel formation at several stages in the angiogenic cascade［7，8］. Other underlying anticancer mechanisms of 2ME2 have been suggested，including inhibition of tubulin polymerization［9，10］，sulfonation of 2ME2［11］，and inhibit