Curcumin in combination with bortezomib synergistically induced apoptosis in human multiple myeloma U266 cells
Curcumin in combination with bortezomib synergistically induced apoptosis in human multiple myeloma U266 cells
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DOI：
10.1016/j.molonc.2008.09.006
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发表时间：
2008-12-01
影响因子：
6.6
通讯作者：
Yoon, Sung-Soo
中科院分区：
文献类型：
--
作者：
Park, Juwon;Ayyappan, Vasudevan;Yoon, Sung-Soo
多发性骨髓瘤细胞的生长受到来自宿主骨髓微环境的各种因素的控制。多发性骨髓瘤细胞和骨髓基质细胞（BMSC）之间的相互作用在粘附分子的表达和生长因子的分泌中起重要作用，所述生长因子参与多发性骨髓瘤（MM）细胞的生长、存活和对抗癌药物的抗性。最近，已经讨论了开发针对MM细胞和MM细胞-BMSC相互作用的新型抗癌治疗策略的可能性。在这里，我们提出的数据显示，姜黄素，从植物姜黄的根茎中提取的姜黄化合物的主要成分，有效地减少了MM细胞和BMSC的生长。姜黄素处理后，IL-6/sIL-6 R诱导的STAT 3和Erk磷酸化在共培养的细胞中显著减少。此外，姜黄素抑制MM细胞和BMSC产生促炎细胞因子和VEGF，这些因子与多发性骨髓瘤的进展相关。在姜黄素和硼替佐米的组合治疗中，IL-6/sIL-6 R诱导的STAT 3和Erk磷酸化被有效抑制。此外，与对照相比，这种组合治疗协同抑制与BMSC共培养的MM细胞的生长。综上所述，这些结果表明姜黄素增强硼替佐米在MM中的治疗功效，这表明该组合疗法在MM的临床管理中具有价值。（C）2008欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Growth of multiple myeloma cells is controlled by various factors derived from host bone marrow microenvironments. interaction between multiple myeloma cells and bone marrow stromal cells (BMSCs) plays an important role in the expression of adhesive molecules and secretion of growth factors involved in multiple myeloma (MM) cell growth, survival, and resistance to anticancer drugs. Recently, the possibility of developing novel anticancer therapeutic strategies targeting both MM cells and MM cell-BMSC interactions has been discussed. Here we present data showing that curcumin, a major constituent of turmeric compounds extracted from the rhizomes of the plant Curcuma longa, effectively reduced the growth of MM cells and BMSCs. Upon treatment with curcumin, IL-6/sIL-6R-induced STAT3 and Erk phosphorylation was dramatically reduced in the co-cultured cells. in addition, curcumin inhibited the production of pro-inflammatory cytokines and VEGF, factors that are associated with the progression of multiple myeloma, from both MM cells and BMSCs. In a combination treatment with curcumin and bortezomib, IL-6/sIL-6R-induced STAT3 and Erk phosphorylation was effectively inhibited. Moreover, this combination treatment synergistically inhibited the growth of MM cells co-cultured with BMSCs as compared to controls. Taken together, these results indicate that curcumin potentiates the therapeutic efficacy of bortezomib in MM suggesting this combination therapy to be of value in the clinical management of MM. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.