ATM通过下调MDMX诱导非小细胞肺癌A549细胞的辐射耐药

Q4 Health Professions
R. Xing, J. J. Chen, M. Chen, J. Lian, L. Li, Xiaoping Zhou, R. Liu, Y. Xie, W. Huang, H. Zhao, Y. Zeng
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引用次数: 0

摘要

背景:肿瘤放射抵抗导致放射治疗效率的降低。因此,探索导致放射耐药的细胞机制,寻找潜在的治疗靶点,对提高放射治疗的疗效具有重要意义。本研究旨在探讨共济失调毛细血管扩张突变(ATM)和小鼠双分钟X (MDMX)在非小细胞肺癌A549细胞放射耐药中的作用及其相应的作用机制。材料与方法:用x射线照射非小细胞肺癌A549细胞,在存在或不存在ATM抑制剂的情况下。检测细胞存活、细胞凋亡、细胞增殖、ATM、MDMX mRNA表达及ATM、MDMX、γ-H2AX、Caspase3、Beclin1蛋白表达。结果:抑制剂(KU60019)联合X照射后,A549细胞的集落形成较单独照射组明显减少。与对照组相比,MDMX敲除A549细胞的集落形成显着增加。辐照后,ATM可下调A549细胞中MDMX的表达。辐照导致γ-H2AX表达显著增加,但MDMX敲低使辐照后γ-H2AX表达降低。Caspase3的表达变化与γ-H2AX相同。照射导致Beclin1表达显著增加,MDMX敲低使照射后Beclin1表达增加。结论:本研究表明,ATM通过下调MDMX的表达诱导了A549细胞的辐射抗性,这至少与A549细胞自噬的激活和DNA损伤的减少有一定的关联。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ATM induces radioresistance of non-small cell lung cancer A549 cells by downregulation of MDMX
Background: Tumor radioresistance leads to a reduction in the efficiency of radiation therapy. It is very important to explore the cellular mechanisms leading to radioresistance and to find potential therapeutic targets, which might improve the efficacy of radiation therapy. This study was to investigate the role of ataxia-telangiectasia mutated (ATM) and murine double minute X (MDMX) in radioresistance in non-small cell lung cancer A549 cells and their corresponding mechanisms of action. Materials and Methods: Non-small cell lung cancer A549 cells were irradiated with X-rays in the presence or absence of ATM inhibitor. Cell survival, cell apoptosis, cell proliferation, mRNA of ATM and MDMX, and protein expression of ATM, MDMX, γ-H2AX, Caspase3, and Beclin1 were measured. Results: After the inhibitor (KU60019) treatment combined with X irradiation, the A549 cells showed a significant decrease in colony formations compared to the group received irradiation alone. The MDMX knockdown A549 cells showed a significant increase in colony formations compared to the control group. ATM downregulated the expression of MDMX after irradiation treatment in A549 cells. Irradiation led to a significant increase in γ-H2AX expression, but MDMX knockdown decreased the γ-H2AX expression after irradiation. The change of Caspase3 expression was the same as γ-H2AX. Irradiation led to a significant increase of Beclin1 expression and MDMX knockdown increased the Beclin1 expression after irradiation. Conclusion: This study indicated that ATM induced radioresistance through downregulating the expression of MDMX, which was at least partly associated with the activation of autophagy and the decrease of DNA damage in A549 cells.
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来源期刊
Iranian Journal of Radiation Research
Iranian Journal of Radiation Research RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
CiteScore
0.67
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Iranian Journal of Radiation Research (IJRR) publishes original scientific research and clinical investigations related to radiation oncology, radiation biology, and Medical and health physics. The clinical studies submitted for publication include experimental studies of combined modality treatment, especially chemoradiotherapy approaches, and relevant innovations in hyperthermia, brachytherapy, high LET irradiation, nuclear medicine, dosimetry, tumor imaging, radiation treatment planning, radiosensitizers, and radioprotectors. All manuscripts must pass stringent peer-review and only papers that are rated of high scientific quality are accepted.
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