Reversible Increase in Resistance of A-431 Carcinoma Cells to TRAIL-Induced Apoptosis in Confluent Cultures Corresponds to a Decrease in Expression of DR4 and DR5 Receptors

R. S. Fadeev, N. V. Dolgikh, A. V. Chekanov, A. S. Senotov, K. S. Krasnov, M. I. Kobyakova, Ya. V. Lomovskaya, I. S. Fadeeva, V. S. Akatov
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Abstract

TRAIL (TNF alpha Related Apoptosis Inducing Ligand) cytokine is of great interest for the development of targeted antitumor drugs. We have previously found a reversible increase in tumour cell resistance to TRAIL-induced apoptosis in confluent cultures. In this work we show that increase in resistance of A-431 cells to TRAIL-induced death in confluent culture is associated with reduced expression of pro-apoptotic receptors DR4 and DR5 with absence of anti-apoptotic receptors DcR1 and DcR2 on cell surface. Decreased representation of DR4 and DR5 receptors on the cell surface is accompanied by a lack of activation of the pro-apoptotic protein Bid, effector caspase 3 under the action of recombinant protein izTRAIL, which leads to an increase in TRAIL resistance. Our results indicate that reversible increase in resistance of human carcinoma A-431 cells to TRAIL-induced apoptosis in confluent cultures is caused by decrease in expression of DR4 and DR5 receptors on cell surface.

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在融合培养中,a -431癌细胞对trail诱导的凋亡的抗性可逆增加,对应于DR4和DR5受体的表达降低
trail (TNF α相关凋亡诱导配体)细胞因子对靶向抗肿瘤药物的开发具有重要意义。我们之前发现,在融合培养中,肿瘤细胞对trail诱导的细胞凋亡的抗性可逆增加。在本研究中,我们发现A-431细胞在融合培养中对trail诱导的死亡的抗性增加与促凋亡受体DR4和DR5的表达减少以及细胞表面抗凋亡受体DcR1和DcR2的缺失有关。DR4和DR5受体在细胞表面的表达减少,同时在重组蛋白izTRAIL的作用下,促凋亡蛋白Bid、效应caspase 3缺乏活化,导致TRAIL抗性增加。我们的研究结果表明,在融合培养中,人癌A-431细胞对trail诱导的凋亡的抗性可逆增加是由细胞表面DR4和DR5受体表达减少引起的。
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CiteScore
1.40
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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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