Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
Institute of Science and Engineering, Kanazawa University, Kanazawa, Japan.
Electromagn Biol Med. 2022 Jul 3;41(3):343-351. doi: 10.1080/15368378.2022.2095645. Epub 2022 Jul 5.
Previous studies reported that combined effect of magnetic field (MF) on cytotoxic drugs in human cancer cells. We focused on the effects of 60 Hz MF on drug activity in human uterine sarcoma MES-SA and drug-resistant variant MES-SA/Dx5 cells that overexpressed the membrane protein MDR1(P-glycoprotein), a drug efflux transporter for doxorubicin, daunorubicin, and etoposide, but not cisplatin. The cisplatin with MF caused 60% decrease in cell viability when compared with no MF treatment, cisplatin alone in MES-SA cells. Even in MES-SA/Dx5 cells, MF exposure equally enhanced cisplatin activity. Then, MF enhanced doxorubicin and daunorubicin activity in MES-SA cells and caused 60% decrease in the cell viability compared with these drugs only but had less effect on these drugs in MES-SA/Dx5 cells. Etoposide activity was unaffected by MF exposure in both cell lines, although etoposide is a MDR1 substrate as with doxorubicin and daunorubicin. Thus, MF had no direct impact on MDR1 in the cell membrane. However, the differences in doxorubicin and daunorubicin activity between MES-SA and MES-SA/Dx5 data revealed that the presence of MDR1 in abundance prevented the enhancing effects of MF on doxorubicin and daunorubicin activity. These results suggested that MF may act in the opposite direction of MDR1, affect the drug influx transporters for doxorubicin and daunorubicin, and facilitate anticancer drug uptake into the cells.
先前的研究报道了磁场（MF）对人类癌细胞细胞毒性药物的联合作用。我们专注于 60 Hz MF 对人子宫肉瘤 MES-SA 及其耐药变体 MES-SA/Dx5 细胞中药物活性的影响，这些细胞过度表达了膜蛋白 MDR1（P-糖蛋白），这是一种用于阿霉素、柔红霉素和依托泊苷的药物外排转运蛋白，但不是顺铂。与无 MF 处理相比，MF 使顺铂对细胞活力的影响降低了 60%，单独使用顺铂时在 MES-SA 细胞中。即使在 MES-SA/Dx5 细胞中，MF 暴露同样增强了顺铂的活性。然后，MF 增强了 MES-SA 细胞中阿霉素和柔红霉素的活性，并使细胞活力降低了 60%，而与这些药物单独使用相比，但对 MES-SA/Dx5 细胞中的这些药物影响较小。MF 暴露对两种细胞系中的依托泊苷活性均无影响，尽管依托泊苷是 MDR1 底物，与阿霉素和柔红霉素一样。因此，MF 对细胞膜中的 MDR1 没有直接影响。然而，MES-SA 和 MES-SA/Dx5 数据中阿霉素和柔红霉素活性的差异表明，大量存在的 MDR1 阻止了 MF 对阿霉素和柔红霉素活性的增强作用。这些结果表明，MF 可能与 MDR1 作用相反，影响阿霉素和柔红霉素的药物内流转运蛋白，并促进抗癌药物进入细胞。
