The short-term effect of histone deacetylase inhibitors, chidamide and valproic acid, on the NF‑κB pathway in multiple myeloma cells.
The short-term effect of histone deacetylase inhibitors, chidamide and valproic acid, on the NF‑κB pathway in multiple myeloma cells.
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DOI：
10.3892/ijmm.2018.3963
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发表时间：
2019-01
影响因子：
5.4
通讯作者：
Fu R
中科院分区：
文献类型：
--
作者：
Liu Z;Jing Q;Wang Y;Li Y;Mi F;Xiang C;Fu R
关于组蛋白脱乙酰酶（HDAC）抑制剂（HDACis）的研究已经引起了对多发性骨髓瘤（MM）治疗的兴趣。此外，MM细胞核因子（NF）-κB的高表达被认为是MM发生、发展的重要因素。本研究旨在探讨HDACis、西达米特和丙戊酸（VPA）对MM细胞的短期作用、对NF-κB的影响及其机制。本研究测定了HDAC活性，以及不同浓度的西达米特和VPA处理6和48 h后U266和RPMI 8226 MM细胞的增殖和凋亡。Western blotting法检测U266和RPMI 8226细胞经西达米特和VPA处理后0、2、4和6 h磷酸化（p）-IκB激酶（IKK）α/β、NF-κB p65和NF-κB抑制因子（IκBα）的表达水平。结果表明，西达米特和丙戊酸钠在6 h时对HDAC活性、细胞增殖和凋亡无明显影响，而在48 h时可抑制HDAC活性和细胞增殖，诱导细胞凋亡。IκBα表达水平随时间逐渐升高，NF-κB p65表达水平随时间逐渐降低。这些结果表明，HDACis chidamine和VPA长期（48 h）处理可抑制MM细胞的增殖并促进其凋亡;但这些HDACis在短期（6 h）内对细胞增殖和凋亡的影响不大。值得注意的是，在短期内（2-6 h），通过IκBα-NF-κB p65途径抑制NF-κB的过度活化。提示HDACis联合其他药物治疗MM时，早期阻断NF-κB通路可抑制细胞生长，增加药物敏感性。
Research regarding histone deacetylase (HDAC) inhibitors (HDACis) has garnered interest for the treatment of multiple myeloma (MM). In addition, the high expression of nuclear factor (NF)-κB in MM cells is considered an important factor in the occurrence and development of MM. The present study aimed to determine the short-term effects of HDACis, chidamide and valproic acid (VPA), on MM cells, their effects on NF-κB and the underlying mechanisms. The present study measured HDAC activity, and the proliferation and apoptosis of U266 and RPMI8226 MM cells following treatment with various concentrations of chidamide and VPA for 6 and 48 h. Western blotting was used to detect the expression levels of phosphorylated (p)-IκB kinase (IKK)α/β, NF-κB p65 and inhibitor of NF-κB (IκBα) in U266 and RPMI8226 cells at various time points following treatment with chidamide and VPA (0, 2, 4 and 6 h). The results revealed that chidamide and VPA had no significant effect on the HDAC activity, proliferation and apoptosis of cells at 6 h; however, cell HDAC activity and proliferation were inhibited, and apoptosis was induced at 48 h. Furthermore, the expression levels of IκBα were gradually increased over time, whereas the expression levels of NF-κB p65 gradually decreased. These findings indicated that long-term (48 h) treatment with the HDACis chidamide and VPA inhibited the proliferation and promoted the apoptosis of MM cells; however, these HDACis had little effect on cell proliferation and apoptosis in the short term (6 h). Notably, in the short term (2-6 h), hyperactivation of NF-κB was inhibited via the IκBα-NF-κB p65 pathway. These findings indicated that cell growth may be inhibited and drug susceptibility may be promoted by blocking the NF-κB pathway at an early stage, when HDACis are combined with other drugs in the treatment of MM.
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影响因子：
20.3
作者：
Bharti, AC;Shishodia, S;Aggarwal, BB
通讯作者：
Aggarwal, BB
影响因子：
7.3
作者：
Kannaiyan, Radhamani;Hay, Hui Sin;Sethi, Gautam
通讯作者：
Sethi, Gautam
影响因子：
5.8
作者：
Chen XY;Li S;Vetica F;Kumar M;Enders D
通讯作者：
Enders D
DOI：
10.1016/j.bbrc.2010.01.011
发表时间：
2010-02-05
影响因子：
3.1
作者：
Liu, Lin;Chen, Baoan;Zhao, Hong
通讯作者：
Zhao, Hong
影响因子：
11.4
作者：
Göttlicher, M;Minucci, S;Heinzel, T
通讯作者：
Heinzel, T