Salamanca-Ortiz Harold, Domínguez-Gomez Guadalupe, Chávez-Blanco Alma, Ortega-Bernal Daniel, Díaz-Chávez José, González-Fierro Aurora, Candelaria-Hernández Myrna, Dueñas-González Alfonso
Subdirection of Basic Research, Instituto Nacional de Cancerología (INCan) Tlalpan, Mexico City 14080, Mexico.
Subdirección de Investigación Clínica, Instituto Nacional de Cancerología (INCan) Tlalpan, Mexico City 14080, Mexico.
Am J Cancer Res. 2024 Jun 15;14(6):3068-3082. doi: 10.62347/IDKG8587. eCollection 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.
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DNA甲基转移酶抑制剂（DNMTi）和组蛋白去乙酰化酶抑制剂（HDACi）药物的潜力。这些药物针对导致淋巴瘤发生和治疗耐药性的细胞过程。我们的研究评估了两种此类药物，肼屈嗪（DNMTi）和丙戊酸盐（HDACi）联合使用对B细胞和T细胞淋巴瘤细胞系的有效性。在此我们表明，随着时间的推移，肼屈嗪和丙戊酸盐的联合使用降低了细胞活力，导致B细胞和T细胞的细胞周期停滞和凋亡。事实证明，这种药物组合具有协同作用，每种药物单独使用时均显示出显著的生长抑制作用。对HuT 78和Raji细胞进行的微阵列分析表明，肼屈嗪和丙戊酸盐的组合分别导致562个和850个基因上调，同时下调152个和650个基因。发现几个促凋亡和细胞周期相关基因上调。值得注意的是，HuT 78细胞和Raji细胞中上调幅度最大的十个基因中，分别有三个和五个与免疫功能相关。总之，我们的研究表明，肼屈嗪和丙戊酸盐的组合是治疗B淋巴瘤和T淋巴瘤的有效选择。这些发现非常令人鼓舞，我们敦促进行进一步的临床评估，以验证我们的研究并有可能改善淋巴瘤的治疗。
