研究动态
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表观遗传再利用药物肼屈嗪和丙戊酸在淋巴瘤细胞中的抑制和转录作用。

The inhibitory and transcriptional effects of the epigenetic repurposed drugs hydralazine and valproate in lymphoma cells.

发表日期:2024
作者: Harold Salamanca-Ortiz, Guadalupe Domínguez-Gomez, Alma Chávez-Blanco, Daniel Ortega-Bernal, José Díaz-Chávez, Aurora González-Fierro, Myrna Candelaria-Hernández, Alfonso Dueñas-González
来源: Epigenetics & Chromatin

摘要:

淋巴瘤是一种每年影响无数生命的疾病。为了对抗这种疾病,研究人员一直在探索 DNMTi 和 HDACi 药物的潜力。这些药物针对导致淋巴瘤发生和治疗耐药的细胞过程。我们的研究评估了肼苯哒嗪 (DNMTi) 和丙戊酸 (HDACi) 这两种药物的组合在 B 细胞和 T 细胞淋巴瘤细胞系中的有效性。在这里,我们发现肼苯哒嗪和丙戊酸的组合随着时间的推移会降低细胞的活力,导致 B 细胞和 T 细胞的细胞周期停滞和细胞凋亡。这种药物组合被证明具有协同作用,每种药物单独显示出显着的生长抑制作用。 HuT 78 和 Raji 细胞的微阵列分析表明,肼屈嗪和丙戊酸盐的组合分别导致 562 和 850 个基因上调,同时下调 152 和 650 个基因。发现一些促凋亡和细胞周期相关基因上调。值得注意的是,HuT 78 和 Raji 细胞中 10 个上调最多的基因中分别有 3 个和 5 个与免疫功能相关。总之,我们的研究表明肼屈嗪和丙戊酸的组合是 B 淋巴瘤和 T 淋巴瘤的有效治疗选择。这些发现非常令人鼓舞,我们敦促进一步进行临床评估,以验证我们的研究并可能改善淋巴瘤治疗。AJCR 版权所有 © 2024。
Lymphoma is a disease that affects countless lives each year. In order to combat this disease, researchers have been exploring the potential of DNMTi and HDACi drugs. These drugs target the cellular processes that contribute to lymphomagenesis and treatment resistance. Our research evaluated the effectiveness of a combination of two such drugs, hydralazine (DNMTi) and valproate (HDACi), in B-cell and T-cell lymphoma cell lines. Here we show that the combination of hydralazine and valproate decreased the viability of cells over time, leading to the arrest of cell-cycle and apoptosis in both B and T-cells. This combination of drugs proved to be synergistic, with each drug showing significant growth inhibition individually. Microarray analyses of HuT 78 and Raji cells showed that the combination of hydralazine and valproate resulted in the up-regulation of 562 and 850 genes, respectively, while down-regulating 152 and 650 genes. Several proapoptotic and cell cycle-related genes were found to be up-regulated. Notably, three and five of the ten most up-regulated genes in HuT 78 and Raji cells, respectively, were related to immune function. In summary, our study suggests that the combination of hydralazine and valproate is an effective treatment option for both B- and T-lymphomas. These findings are highly encouraging, and we urge further clinical evaluation to validate our research and potentially improve lymphoma treatment.AJCR Copyright © 2024.