Dou Jun, Mei Feng, Xu Hui, Rui Xue, Bao Xueyang, Liu Kena, Zhao Fengsu
Academic Affairs Office, Xinjiang Second Medical College, Karamay, Xinjiang Ugur Autonomous Region, China.
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Front Oncol. 2025 Sep 3;15:1515956. doi: 10.3389/fonc.2025.1515956. eCollection 2025.
Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults. While conventional therapies can induce remission disease frequently relapses with fatal outcomes. This study aimed to explore the inhibitory effect of iron oxide nanoparticles (IONPs) combined with cytarabine (Ara-C) on AML by modulating the interferon-induced transmembrane protein 3 (IFITM3) expression of in KG-1a cells and AML-bearing mice.
A lentiviral vector targeting (LV-shIFITM3) was used to transduce human AML KG-1a cells, and the biological effects of IFITM3 knockdown were assessed. NOD/SCID mice were engrafted with LV-shIFITM3-KG1a cells and their survival status as well as abnormal cell population were monitored.
Compared to control cells, IFITM3 expression level in the LV-shIFITM3 transduced KG-1a cells exhibited reduced IFITM3 expression, leading to suppressed proliferation, impaired clonogenicity, cell cycle arrest, and increased apoptosis. The combination of IONPs and Ara-C further diminished IFITM3 level, inhibited KG-1a proliferation, and induced apoptosis while elevating reactive oxygen species (ROS) production. , IONPs plus Ara-C treatment reduced immature granulocytes in peripheral blood and bone marrow, downregulated AML-associated markers (clustered differentiation(CD)33 and CD11b), and ameliorated disease progression in AML-bearing mice compared to controls.
IFITM3 knockdown in KG-1a cells inhibited proliferation and promoted apoptosis. The combination of IONPs and Ara-C may represent a promising therapeutic strategy for AML by suppressing IFITM3 expression, enhancing ROS levels, and inducing apoptosis. These findings suggest IFITM3 as a potential molecular target and highlight the synergistic efficacy of IONPs and Ara-C in AML treatment.
急性髓系白血病（AML）是成人中最常见的急性白血病。虽然传统疗法可诱导缓解，但疾病常复发并导致致命后果。本研究旨在通过调节干扰素诱导跨膜蛋白3（IFITM3）在KG-1a细胞和荷AML小鼠中的表达，探讨氧化铁纳米颗粒（IONPs）联合阿糖胞苷（Ara-C）对AML的抑制作用。
使用靶向IFITM3的慢病毒载体（LV-shIFITM3）转导人AML KG-1a细胞，并评估IFITM3基因敲低的生物学效应。将LV-shIFITM3-KG1a细胞移植到NOD/SCID小鼠体内，监测其生存状态以及异常细胞群体。
与对照细胞相比，LV-shIFITM3转导的KG-1a细胞中IFITM3表达水平降低，导致增殖受抑、克隆形成能力受损、细胞周期停滞和凋亡增加。IONPs与Ara-C联合使用进一步降低了IFITM3水平，抑制了KG-1a增殖并诱导凋亡，同时提高了活性氧（ROS）的产生。此外，与对照组相比，IONPs加Ara-C治疗减少了外周血和骨髓中的未成熟粒细胞，下调了AML相关标志物（分化簇（CD）33和CD11b），并改善了荷AML小鼠的疾病进展。
KG-1a细胞中IFITM3基因敲低抑制了增殖并促进了凋亡。IONPs与Ara-C联合使用可能是一种有前景的AML治疗策略，通过抑制IFITM3表达、提高ROS水平和诱导凋亡来实现。这些发现表明IFITM3是一个潜在的分子靶点，并突出了IONPs与Ara-C在AML治疗中的协同疗效。
