Xiang Huaguo, Sun Junfang, Kong Lingyue, Wang Yingzhen, Qiu Xiaorou, Zeng Jinting, Li Guo, He Jiehong
Department of Clinical Laboratory, Fuyong People's Hospital of Baoan District, 81 Defeng Road, Fuyong Street, Shenzhen, 518103, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 8. doi: 10.1007/s00210-025-04237-1.
Cervical cancer (CC) ranks among the primary causes of cancer fatalities in women, with cisplatin (DDP) resistance significantly impacting clinical outcomes. NADH dehydrogenase (ubiquinone) FA8 (NDUFA8) is significantly upregulated in CC tissues and correlates with lower survival rates, but its role in cisplatin sensitivity in CC is still unclear. NDUFA8 silencing inhibited CC cell viability, promoted ferroptosis, evidenced by increased Fe and lipid ROS levels, along with decreased levels of ATP and reduced activities of complex I, aconitase (ACO), and xanthine oxidase (XO). However, overexpression of NDUFA8 promoted CC cell viability, inhibited ferroptosis, and increased levels of ATP and activities of complex I, ACO, and XO in ferric ammonium citrate (FAC) or rotenone-treated CC cells. NDUFA8 expression showed a negative correlation with the DDP therapy response in CC tissues and cell lines. However, in CC tissues, NDUFA8 expression was positively associated with ACO and XO activities. In in vivo experiments, the overexpression of NDUFA8 diminished the anti-tumor effects of DDP, which was counteracted by FAC. NDUFA8 promotes cell viability and inhibits ferroptosis and DDP sensitivity by stabilizing Fe-S clusters in CC.
宫颈癌（CC）是女性癌症死亡的主要原因之一，顺铂（DDP）耐药性对临床结果有显著影响。NADH脱氢酶（泛醌）FA8（NDUFA8）在CC组织中显著上调，且与较低的生存率相关，但其在CC顺铂敏感性中的作用仍不清楚。NDUFA8沉默抑制CC细胞活力，促进铁死亡，表现为铁和脂质活性氧水平升高，同时ATP水平降低，以及复合物I、乌头酸酶（ACO）和黄嘌呤氧化酶（XO）的活性降低。然而，NDUFA8过表达促进CC细胞活力，抑制铁死亡，并在柠檬酸铁铵（FAC）或鱼藤酮处理的CC细胞中增加ATP水平以及复合物I、ACO和XO的活性。NDUFA8表达在CC组织和细胞系中与DDP治疗反应呈负相关。然而，在CC组织中，NDUFA8表达与ACO和XO活性呈正相关。在体内实验中，NDUFA8过表达减弱了DDP的抗肿瘤作用，而FAC可抵消这种作用。NDUFA8通过稳定CC中的铁硫簇促进细胞活力、抑制铁死亡和DDP敏感性。
