HPOB 通过转录激活 p21 对多发性骨髓瘤细胞的抗增殖活性。
Anti-Proliferative Activity of HPOB against Multiple Myeloma Cells via p21 Transcriptional Activation.
机构信息
College of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.
出版信息
Molecules. 2018 Apr 30;23(5):1044. doi: 10.3390/molecules23051044.
Histone acetylation or deacetylation is closely associated with the progression of multiple myeloma (MM). Currently, many histone deacetylase (HDAC) inhibitors have been approved for being used in clinical trials, but theirtherapeutic effectsarestill not ideal. As a novel HDAC inhibitor, hydroxamicacid-based small-molecule-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB)’s possible roles in MM have not been studied. In this present study, the effect of HPOB as a potential anti-tumor agent in preventingproliferation and inducing apoptosis of MM cells had been investigated in detail. Our results showed that HPOB decreased the survival of MM cells in dose- and time-dependent manner. In addition, HPOB caused the accumulation of MM cells in G1 phase compared with the dimethylsulfoxide (DMSO) control group. Interestingly, we found that HPOB could overcome bortezomib (BTZ) resistance inMM cells and combining HPOB with BTZ could further sensitize MM cells. Certainly, our data illuminated that HPOB-mediated cell death occurs via transcriptional activation of p21, which was associated with an elevated level of global histone 3 acetylation (H3Ac) modification. Therefore, HPOB could be a potential candidate for MM treatment and the combination of HPOB and bortezomibcould bea possible therapeutic strategy for relapsed and refractory MM.
组蛋白乙酰化或去乙酰化与多发性骨髓瘤（MM）的进展密切相关。目前，许多组蛋白去乙酰化酶（HDAC）抑制剂已被批准用于临床试验，但它们的治疗效果仍不理想。作为一种新型的 HDAC 抑制剂，基于羟肟酸的小分子-4-（2-[(2-羟乙基）（苯基）氨基]-2-氧代乙基）苯甲酰胺（HPOB）在 MM 中的作用尚未得到研究。在本研究中，详细研究了 HPOB 作为潜在的抗肿瘤药物在预防 MM 细胞增殖和诱导细胞凋亡中的作用。我们的结果表明，HPOB 以剂量和时间依赖的方式降低 MM 细胞的存活率。此外，与二甲基亚砜（DMSO）对照组相比，HPOB 导致 MM 细胞在 G1 期积累。有趣的是，我们发现 HPOB 可以克服 MM 细胞中的硼替佐米（BTZ）耐药性，并且 HPOB 与 BTZ 联合使用可以进一步使 MM 细胞敏感。当然，我们的数据表明，HPOB 介导的细胞死亡是通过 p21 的转录激活发生的，这与全局组蛋白 3 乙酰化（H3Ac）修饰水平的升高有关。因此，HPOB 可能是 MM 治疗的潜在候选药物，HPOB 和硼替佐米的联合使用可能是复发性和难治性 MM 的一种潜在治疗策略。
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