Differentiation induction enhances bortezomib efficacy and overcomes drug resistance in multiple myeloma
Differentiation induction enhances bortezomib efficacy and overcomes drug resistance in multiple myeloma
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DOI：
10.1016/j.bbrc.2012.03.056
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发表时间：
2012-04-13
影响因子：
3.1
通讯作者：
Su, Chang
中科院分区：
文献类型：
--
作者：
Gu, Jing-li;Li, Juan;Su, Chang
目的：寻找克服硼替佐米耐药的方法具有重要的临床意义。本研究旨在阐明骨髓瘤细胞对硼替佐米的耐药性与其分化状态之间的关系，并探讨诱导分化克服骨髓瘤细胞硼替佐米耐药性的可行性。方法：采用细胞形态学、免疫球蛋白轻链蛋白分泌水平和XBP-1表达水平评价骨髓瘤细胞的分化状态。结果：骨髓瘤细胞的分化状态与骨髓瘤对硼替佐米的敏感性有关。成功诱导分化后，骨髓瘤细胞对硼替佐米更敏感，生长减慢，凋亡率增加。诱导分化通过增加免疫球蛋白分泌增加骨髓瘤细胞中蛋白酶体的工作量，同时通过降低蛋白酶体活性降低蛋白酶体的能力。蛋白酶体工作量增加和蛋白酶体能力下降之间的不平衡是一个可能的机制，诱导分化克服骨髓瘤耐药性bortezavalin.Conclusion：目前的研究表明，第一次，骨髓瘤分化状态与骨髓瘤敏感性bortezavalin. The诱导分化可以克服骨髓瘤耐药性bortezavalin. Conclusion。(C)2012 Elsevier Inc. All rights reserved.
Aim: It is of clinical importance to find methods to overcome bortezomib resistance. In the current study, we clarified the relationship between resistance to bortezomib and the differentiation status of myeloma cells, and explored the feasibility of induction of differentiation in overcoming bortezomib resistance in myeloma.Methods: Cell morphology, immunoglobulin light-chain protein secretion levels, and XBP-1 expression were used to evaluate the differentiation status of myeloma cells. Low dose 2-ME2 alone or in combination with ATRA was used to induce differentiation in myeloma cells.Results: The differentiation status of myeloma cells was related to myeloma sensitivity to bortezomib. After successful induction of differentiation, the myeloma cells were more sensitive to bortezomib with decreased growth and an increased rate of apoptosis. Induction of differentiation increased the proteasome workload in myeloma cells by increasing immunoglobulin secretion, while reducing proteasome capacity by decreasing proteasome activity. The imbalance between increased proteasome workload and decreased proteasome capacity is a possible mechanism by which induction of differentiation overcomes myeloma resistance to bortezomib.Conclusion: The current study demonstrated, for the first time, that myeloma differentiation status is associated with myeloma sensitivity to bortezomib and that induction of differentiation can overcome myeloma resistance to bortezomib. (C) 2012 Elsevier Inc. All rights reserved.