髓系分化通过降低DR4和DR5受体的表达增加白血病细胞对trail诱导的死亡的抵抗力

Ya. V. Lomovskaya, M. I. Kobyakova, A. S. Senotov, I. S. Fadeeva, A. I. Lomovsky, K. S. Krasnov, D. Yu. Shtatnova, V. S. Akatov, R. S. Fadeev
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引用次数: 0

摘要

肿瘤细胞抵抗trail诱导死亡的机制研究仍然是一项紧迫的任务,因为这种细胞因子是抗肿瘤免疫的重要高选择性分子效应。我们的研究表明,人白血病细胞THP-1、HL-60和K562通过降低细胞表面DR4和DR5受体的表达,在体外诱导除红细胞外的髓系分化的所有方向上,外源因子诱导THP-1、HL-60和K562对trail诱导的死亡的抵抗能力增强。研究还发现,ONC 201、tunicamycin和SAHA(羟肟酸亚eroylanilide)能够引起白血病细胞中DR5表达的增加,从而抑制分化因子诱导的白血病细胞对TRAIL的抵抗。所获得的结果对开发药物和策略以提高治疗髓性白血病的有效性具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Myeloid Differentiation Increases Resistance of Leukemic Cells to TRAIL-Induced Death by Reducing the Expression of DR4 and DR5 Receptors

The study of the mechanisms of resistance of tumor cells to TRAIL-induced death remains an urgent task since this cytokine is an important highly selective molecular effector of antitumor immunity. Our study showed that human leukemia cells THP-1, HL-60, and K562 increased their resistance to TRAIL-induced death in vitro as a result of induction of myeloid differentiation in them by exogenous factors in all directions of myelopoiesis, except for erythroid, by reducing the expression of DR4 and DR5 receptors on the cell surface. It was also found that ONC 201, tunicamycin, and SAHA (hydroxamic acid suberoylanilide), capable of causing an increase in the expression of DR5 in leukemic cells, suppressed their TRAIL resistance induced by differentiation factors. The results obtained are of interest for the development of drugs and strategies to improve the effectiveness of the treatment of myeloid leukemia.

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来源期刊
CiteScore
1.40
自引率
0.00%
发文量
28
期刊介绍: Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology   is an international peer reviewed journal that publishes original articles on physical, chemical, and molecular mechanisms that underlie basic properties of biological membranes and mediate membrane-related cellular functions. The primary topics of the journal are membrane structure, mechanisms of membrane transport, bioenergetics and photobiology, intracellular signaling as well as membrane aspects of cell biology, immunology, and medicine. The journal is multidisciplinary and gives preference to those articles that employ a variety of experimental approaches, basically in biophysics but also in biochemistry, cytology, and molecular biology. The journal publishes articles that strive for unveiling membrane and cellular functions through innovative theoretical models and computer simulations.
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