BCLAF1 对 HDAC 抑制剂 LMK-235 介导的弥漫性大 B 细胞淋巴瘤细胞凋亡的影响及其机制。
Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism.
机构信息
a Guizhou Medical University , Guiyang , Guizhou , China.
d Guizhou Province Laboratory of Haematopoietic Stem Cell Transplantation Center , Guiyang , Guizhou , China.
出版信息
Cancer Biol Ther. 2018;19(9):825-834. doi: 10.1080/15384047.2018.1472188. Epub 2018 Jul 3.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult lymphoma. It is a group of malignant tumors with a large number of clinical manifestations and prognoses. Therefore, it is necessary to explore its unknown potential therapeutic targets. Histone deacetylase inhibitor (HDACi) is a novel drug for the treatment of DLBCL, however pan-HDACis cannot be ignored because of their clinical efficacy. By contrast, specific HDACi is well-tolerated, and LMK-235 is a novel HDACi that is a specific inhibitor of HDAC4 and HDAC5. In this study, we investigated the up-regulation of BCLAF1 through NF-κB signaling pathways in LMK-235, mediating the apoptosis of two diffuse large B-cell lymphoma cell lines, OCI-LY10 and OCI-LY3. Further studies showed that BCLAF1 expression was increased in DLBCL cells after treatment with the NF-κB inhibitor Bay11-7082. The combination of Bay11-7082 and siRNA si-HDAC4 significantly increased BCLAF1 expression and further increased apoptosis. These results indicate that BCLAF1 plays an important role in LMK-235-mediated apoptosis and may be a potential target for the treatment of diffuse large B-cell lymphoma.
弥漫性大 B 细胞淋巴瘤（DLBCL）是成人淋巴瘤中最常见的类型。它是一组临床表现和预后差异较大的恶性肿瘤。因此，有必要探索其未知的潜在治疗靶点。组蛋白去乙酰化酶抑制剂（HDACi）是治疗 DLBCL 的新型药物，但 pan-HDACi 因其临床疗效而不容忽视。相比之下，特异性 HDACi 具有良好的耐受性，而 LMK-235 是一种新型的 HDACi，它是 HDAC4 和 HDAC5 的特异性抑制剂。在这项研究中，我们通过 NF-κB 信号通路研究了 LMK-235 上调 BCLAF1 在两种弥漫性大 B 细胞淋巴瘤细胞系 OCI-LY10 和 OCI-LY3 中的作用，介导其凋亡。进一步的研究表明，NF-κB 抑制剂 Bay11-7082 处理后，DLBCL 细胞中 BCLAF1 的表达增加。Bay11-7082 和 siRNA si-HDAC4 的联合使用显著增加了 BCLAF1 的表达，并进一步增加了细胞凋亡。这些结果表明，BCLAF1 在 LMK-235 介导的凋亡中起重要作用，可能是治疗弥漫性大 B 细胞淋巴瘤的潜在靶点。
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