ORIGINAL RESEARCH article
Front. Oncol.
Sec. Hematologic Malignancies
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1515956
IONPs combined with Cytarabine downregulated IFITM3 expression to inhibit Acute Myeloid Leukemia
Provisionally accepted
- 1School of Medicine, Southeast University, Nanjing, China
- 2Southeast University, Nanjing, Jiangsu Province, China
- 3West Yunnan University of Applied Sciences, Dali, Yunnan Province, China
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Background and objective: 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.Methods A lentiviral vector targeting IFITM3 (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. In vivo, 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. Conclusion: 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.
Keywords: Acute Myeloid Leukemia, interferon-induced transmembrane protein 3, Iron oxide nanoparticles, Cytarabine, acute myeloid leukemia-bearing mice acute myeloid leukemia, acute myeloid leukemia-bearing mice
Received: 23 Oct 2024; Accepted: 23 Jul 2025.
Copyright: © 2025 Dou, Mei, Xu, Xue, Bao, Liu and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jun Dou, School of Medicine, Southeast University, Nanjing, China
Fengsu Zhao, School of Medicine, Southeast University, Nanjing, China
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