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Effects of Dimeric Bisbenzimidazoles and Ionizing Radiation on MCF-7 Breast Cancer Stem Cells
Biophysics Pub Date : 2020-01-01 , DOI: 10.1134/s0006350920010030
K. A. Churyukina , A. L. Zhuze , A. A. Ivanov , I. A. Zamulaeva

Abstract —This study aimed to determine how to eliminate and/or increase the radiosensitivity of a population of cancer stem cells that are responsible for radioresistance in malignant neoplasms. The single and combined effects of γ-radiation at a dose of 4 Gy and dimeric bisbenzimidazoles of the DB( n ) series on the cancer stem cells have been studied using the MCF-7 human breast cancer cell line. The DB( n ) molecules contain n (five or seven) methylene groups in the linker between two benzimidazoles. It has been shown that DB(5) significantly reduces the relative and absolute numbers of the cancer stem cells by factors of 5.8 and 7.5, respectively, compared to the control ( p = 0.001 in both cases), and DB(7) reduces the above cell numbers by factors of 3.6 ( p = 0.003) and 5.2 ( p = 0.004), respectively. Irradiation leads to an increase of the relative and absolute numbers of cancer stem cells by factors of 1.7 and 1.6 ( p < 0.05) compared to the control, respectively. The combined effects of DB(5, 7) and ionizing radiation led to a significant decrease in the relative number of cancer stem cells by factors of 8.2 and 4.1, respectively, compared to only the single irradiation ( p = 0.003 and p = 0.004). Even more pronounced outcomes of the combined action of DB(5, 7) and radiation have been found with regard to the absolute number of cancer stem cells, which decreases by factors of 16.6 and 14.1, respectively, compared to those after only single irradiation ( p = 0.006 in both cases). The combined effect of DB(5, 7) and ionizing radiation led to the inhibition of the radiation-induced epithelial-mesenchymal transition as shown by the expression of vimentin, which is one of the markers of this process that plays an important role in the formation of cancer stem cells pool.

中文翻译:

二聚双苯并咪唑和电离辐射对MCF-7乳腺癌干细胞的影响

摘要 —这项研究旨在确定如何消除和/或增加负责恶性肿瘤放射抗性的癌症干细胞群的放射敏感性。已经使用 MCF-7 人乳腺癌细胞系研究了 4 Gy 剂量的 γ 辐射和 DB(n) 系列的二聚体双苯并咪唑对癌症干细胞的单一和联合影响。DB(n) 分子在两个苯并咪唑之间的连接体中包含 n 个(五个或七个)亚甲基。已经表明,与对照相比,DB(5) 分别显着降低了癌症干细胞的相对和绝对数量 5.8 倍和 7.5 倍(两种情况下均为 p = 0.001),并且 DB(7) 降低了分别比细胞数高 3.6 (p = 0.003) 和 5.2 (p = 0.004)。与对照相比,辐射导致癌症干细胞的相对和绝对数量分别增加了 1.7 和 1.6 倍(p < 0.05)。与仅单次照射相比,DB(5, 7) 和电离辐射的联合作用导致癌症干细胞的相对数量显着减少了 8.2 倍和 4.1 倍(p = 0.003 和 p = 0.004) . 已经发现 DB(5, 7) 和辐射的联合作用在癌症干细胞的绝对数量方面更显着,与仅单次照射后相比,癌症干细胞的绝对数量分别减少了 16.6 和 14.1 倍(在这两种情况下,p = 0.006)。DB(5,
更新日期:2020-01-01
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