沉默Tip60基因对于乳腺癌细胞对放疗的反应的影响。
The effect of silencing the Tip60 gene on the response to radiotherapy in breast cancer cells.
发表日期:2023 Apr 13
作者:
Ece Miser-Salihoğlu, Bensu Karahalil, Meriç Arda Eşmakaya, Uğur Tamer, Sevgi Yardim-Akaydin
来源:
BREAST
摘要:
由于三阴性乳腺癌患者不对激素治疗产生反应,主要的治疗方法是化疗和放疗的组合。由于某些化疗药物和放疗的靶点都是肿瘤细胞的DNA,对于具有高DNA修复通路的个体可能会出现问题。研究表明,Tip60基因的高表达会增加肿瘤细胞DNA双链断裂的修复,尤其是在放疗治疗期间,从而降低对治疗的反应并对治疗产生不良影响。本研究首次探讨了在MDA-MB-231和MCF-7细胞中沉默和活性Tip60基因对放疗反应的作用。为此,通过向细胞系应用siRNA来沉默Tip60基因,并施加UV。在研究中,通过MTT和COMET方法测量了细胞系的细胞毒性和DNA断裂,并通过PCR和拉曼分光光度计测量了沉默、未沉默、接受UV处理和未接受UV处理的细胞系的mRNA和蛋白质表达值。根据研究结果,在沉默Tip60基因的MCF-7细胞系中,在施加放疗的情况下观察到了增加的DNA损伤,相比之下Tip60基因活跃的细胞系中DNA损伤减少了。观察到MDA-MB-231细胞系中的DNA损伤要少于Tip60基因活跃的细胞系。版权所有 © 2023 The Authors。Elsevier Ltd.保留所有权利。
Since patients with triple-negative breast cancer do not respond to hormone therapy, the main treatment method is the combination of chemotherapy and radiotherapy. Because the DNA of the tumor cell is the target in both some chemotherapeutics and radiotherapy, problems may occur in individuals with a high DNA repair pathway. It is suggested that high expression of the Tip60 gene, which has an important role in repairing DNA damage, will increase the repair of DNA double-strand breaks in tumor cells, especially during radiotherapy treatment, thus reducing the response to treatment and adversely affecting treatment. In this study, for the first time, the role of the silenced and active Tip60 gene in response to radiotherapy in MDA-MB-231 and MCF-7 cells was investigated. For this purpose, the Tip60 gene was silenced by applying siRNA to the cell lines and UV was applied. In the study, cytotoxicity and DNA breaks were measured by MTT and COMET methods, and mRNA and protein expression values were measured by PCR and Raman spectrophotometer in silenced, unsilenced, UV-treated, and non-UV-treated cell lines. According to the results of the study, increased DNA damage was observed in MCF-7 cell lines in which the Tip60 gene was silenced, and radiotherapy was applied, compared to the cell lines with the Tip60 gene active. It was observed that DNA damage in MDA-MB-231 cell lines was less than in cell lines with the active Tip60 gene.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.