Gazi University, Faculty of Pharmacy, Department of Biochemistry, 06330, Ankara, Türkiye.
Gazi University, Faculty of Pharmacy, Department of Toxicology, 06330, Ankara, Türkiye.
Breast. 2023 Jun;69:507-512. doi: 10.1016/j.breast.2023.04.001. Epub 2023 Apr 13.
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.
由于三阴性乳腺癌患者对激素治疗没有反应,主要的治疗方法是化疗和放疗相结合。由于肿瘤细胞的 DNA 是一些化疗药物和放疗的靶点,因此在 DNA 修复途径较高的个体中可能会出现问题。有研究表明,高表达在修复 DNA 损伤中起重要作用的 Tip60 基因,会增加肿瘤细胞中 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,并对治疗产生不利影响。在这项研究中,首次研究了沉默和激活的 Tip60 基因在 MDA-MB-231 和 MCF-7 细胞对放疗的反应中的作用。为此,通过向细胞系应用 siRNA 沉默 Tip60 基因,并应用 UV。在研究中,通过 MTT 和 COMET 方法测量细胞毒性和 DNA 断裂,以及通过 PCR 和拉曼分光光度计测量沉默、未沉默、UV 处理和非 UV 处理细胞系中的 mRNA 和蛋白质表达值。根据研究结果,与 Tip60 基因活跃的细胞系相比,沉默 Tip60 基因并应用放疗的 MCF-7 细胞系中观察到 DNA 损伤增加。在 MDA-MB-231 细胞系中观察到的 DNA 损伤小于 Tip60 基因活跃的细胞系。