目前的鼻咽癌治疗方法已经提高了患者的5年生存率；然而，一些患者并没有从治疗中受益。因此，必须开发现有的治疗方法或新药物来改善患者的预后。 NAD (P)H:醌氧化还原酶1 (NQO1)是一种在多种癌症中高表达的电子还原酶，可以将氮丙啶基取代的醌衍生化合物转化为烷化剂，导致细胞凋亡。因此，先前设计了一种二氮丙啶基取代的醌衍生化合物AZ-1。本研究探讨AZ-1在NPC细胞中是否具有抗癌活性并探讨其潜在机制。该研究使用NPC-TW01细胞，并使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑进行溴化物、集落形成、末端脱氧核苷酸转移酶 dUTP 缺口末端标记和免疫印迹测定，分别评估细胞活力、细胞存活、DNA 片段化和蛋白质表达。结果表明，AZ-1 显着抑制细胞活力和存活。 NPC-TW01 细胞。 AZ-1 还诱导裂解的 PARP、裂解的 caspase-8、裂解的 caspase-9 和裂解的 caspase-3 的表达，并引发 NPC-TW01 细胞中的 DNA 片段化。此外，AZ-1 在 NPC-TW01 细胞中诱导 DNA 损伤标记 γH2AX 表达。使用 NQO1 活性抑制剂双香豆素治疗，不仅逆转了 AZ-1 诱导的细胞活力抑制，还降低了 AZ-1 诱导的 γH2AX、cleaved caspase-8、cleaved caspase-9 和 cleaved caspase-3 的表达。NQO1 逆转AZ-1 触发细胞活力抑制、DNA 损伤和细胞凋亡。这项研究的结果可能为AZ-1在鼻咽癌治疗中可能的临床应用提供依据，以改善鼻咽癌患者的预后。版权所有 © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All保留权利。

Current NPC treatment methods have improved the 5-year survival rates of patients; however, some patients do not benefit from the treatments. Therefore, the existing treatment methods or new drugs must be developed to improve the patient's prognosis. NAD (P)H:quinone oxidoreductase 1 (NQO1), an electron reductase highly expressed in various cancers, can convert aziridinyl-substituted quinone-derived compound into an alkylating agent, resulting in cell apoptosis. Therefore, a di-aziridinyl-substituted quinone-derived compound, AZ-1, was designed previously. The present study investigated whether AZ-1 has anticancer activities in NPC cells and explored the underlying mechanism.NPC-TW01 cells were used in the study, and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide, colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunoblotting assays were performed to assess the cell viability, cell survival, DNA fragmentation, and protein expression, respectively.The results show that AZ-1 significantly inhibited the viability and survival of NPC-TW01 cells. AZ-1 also induced the expression of cleaved PARP, cleaved caspase-8, cleaved caspase-9, and cleaved caspase-3, and triggered DNA fragmentation in NPC-TW01 cells. In addition, AZ-1 induced γH2AX expression, a DNA damage marker, in NPC-TW01 cells. Treatment with dicoumarol, an NQO1 activity inhibitor, not only reversed AZ-1-induced cell viability inhibition but also decreased AZ-1-induced expression of γH2AX, cleaved caspase-8, cleaved caspase-9, and cleaved caspase-3.NQO1 reverses AZ-1-triggered cell viability inhibition, DNA damage, and apoptosis. The findings of this study may provide a basis for the possible clinical application of AZ-1 in the treatment of NPC to improve the prognosis of patients with NPC.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.