You Hongliang, Wang Dao, Wei Linlin, Chen Jiao, Li Huanhuan, Liu Yufeng
Department of Hematology and Oncology, Children's Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Oncol. 2022 Feb 21;2022:8281267. doi: 10.1155/2022/8281267. eCollection 2022.
Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, with a feature of easy to induce multidrug resistance and relapse. Abundant studies have proved that iron overload strengthens the growth and metastasis of tumor cells. Herein, we found that deferoxamine (DFO) effectively decreased the concentration of intracellular iron in ALL cells. DFO inhibited proliferation, induced apoptosis, and obstructed cell cycle of ALL cells, whereas DFO and dextriferron (Dex) used in combination significantly decreased the sensitivity of ALL cells to DFO. Reactive oxygen species (ROS) level was reduced in ALL cells treated with DFO, and the combination of DFO and Dex reversed the effects of DFO. , DFO inhibited mouse tumor growth. Besides, cyclinD1, -catenin, c-Myc, hypoxia inducible factor 1 (HIF-1), p-p38MAPK, and p-ERK1/2 protein levels were significantly downregulated, and the levels of prolyl hydroxylase-2 (PHD-2) were upregulated after treated with DFO, whereas Dex treatment reversed those and . In conclusion, DFO inhibited the proliferation and ALL xenograft tumor growth, obstructed the cell cycle, and induced apoptosis of ALL cells, probably via inactivating the ROS/HIF-1, Wnt/-catenin, and p38MAPK/ERK signaling.
急性淋巴细胞白血病（ALL）是儿童期最常见的癌症类型，具有易于诱导多药耐药和复发的特点。大量研究证明，铁过载会增强肿瘤细胞的生长和转移。在此，我们发现去铁胺（DFO）能有效降低ALL细胞内铁的浓度。DFO抑制ALL细胞的增殖，诱导其凋亡，并阻碍细胞周期，而DFO与右丙亚胺（Dex）联合使用则显著降低ALL细胞对DFO的敏感性。用DFO处理的ALL细胞中活性氧（ROS）水平降低，DFO与Dex联合使用可逆转DFO的作用。此外，DFO抑制小鼠肿瘤生长。此外，经DFO处理后，细胞周期蛋白D1、β-连环蛋白、c-Myc、缺氧诱导因子1（HIF-1）、磷酸化p38丝裂原活化蛋白激酶（p-p38MAPK）和磷酸化细胞外信号调节激酶1/2（p-ERK1/2）的蛋白水平显著下调，脯氨酰羟化酶-2（PHD-2）水平上调，而Dex处理则逆转了这些变化。总之，DFO可能通过使ROS/HIF-1、Wnt/β-连环蛋白和p38MAPK/ERK信号失活，从而抑制ALL细胞的增殖和异种移植肿瘤生长，阻碍细胞周期，并诱导ALL细胞凋亡。
