Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju, Republic of Korea.
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, U.S.A.
Anticancer Res. 2024 Jul;44(7):2837-2846. doi: 10.21873/anticanres.17096.
BACKGROUND/AIM: Pulsed electromagnetic field (PEMF) stimulation enhances the efficacy of several anticancer drugs. Doxorubicin is an anticancer drug used to treat various types of cancer, including breast cancer. However, the effect of PEMF stimulation on the efficacy of doxorubicin and the underlying mechanisms remain unclear. Thus, this study aimed to investigate the effect of PEMF stimulation on the anticancer activity of doxorubicin in MDA-MB-231 human breast cancer cells.
MDA-MB-231 cells were seeded and allowed to incubate for 48 h. The cells were treated with doxorubicin, cisplatin, 5-fluorouracil, or paclitaxel for 48 h. Subsequently, the cells were stimulated with a 60-min PEMF session thrice a day (with an interval of 4 h between each session) for 24 or 48 h. Cell viability was assessed by trypan blue dye exclusion assay and cell-cycle analysis was analyzed by flow cytometry. Molecular mechanisms involved in late G arrest were confirmed by a western blot assay and confocal microscopy.
MDA-MB-231 cells treated with a combination of doxorubicin and PEMF had remarkably lower viability than those treated with doxorubicin alone. PEMF stimulation increased doxorubicin-induced cell-cycle arrest in the late G phase by suppressing cyclin-dependent kinase 1 (CDK1) activity through the enhancement of myelin transcription factor 1 (MYT1) expression, cell division cycle 25C (CDC25C) phosphorylation, and stratifin (14-3-3σ) expression. PEMF also increased doxorubicin-induced DNA damage by inhibiting DNA topoisomerase II alpha (TOP2A).
These findings support the use of PEMF stimulation as an adjuvant to strengthen the antiproliferative effect of doxorubicin on breast cancer cells.
背景/目的：脉冲电磁场（PEMF）刺激可增强几种抗癌药物的疗效。阿霉素是一种用于治疗多种癌症的抗癌药物，包括乳腺癌。然而，PEMF 刺激对阿霉素疗效的影响及其潜在机制尚不清楚。因此，本研究旨在探讨 PEMF 刺激对 MDA-MB-231 人乳腺癌细胞中阿霉素抗癌活性的影响。
将 MDA-MB-231 细胞接种并孵育 48 小时。用阿霉素、顺铂、5-氟尿嘧啶或紫杉醇处理细胞 48 小时。随后，用 60 分钟的 PEMF 治疗 3 次，每天 1 次（每次治疗之间间隔 4 小时），持续 24 或 48 小时。通过台盼蓝排斥试验评估细胞活力，通过流式细胞术分析细胞周期。通过 Western blot 分析和共聚焦显微镜证实晚期 G1 期阻滞相关的分子机制。
与单独使用阿霉素相比，联合使用阿霉素和 PEMF 的 MDA-MB-231 细胞活力显著降低。PEMF 刺激通过增强髓鞘转录因子 1（MYT1）表达、细胞分裂周期蛋白 25C（CDC25C）磷酸化和层粘连蛋白（14-3-3σ）表达来抑制周期蛋白依赖性激酶 1（CDK1）活性，从而增加阿霉素诱导的晚期 G1 期细胞周期阻滞。PEMF 还通过抑制 DNA 拓扑异构酶 IIα（TOP2A）来增加阿霉素诱导的 DNA 损伤。
这些发现支持使用 PEMF 刺激作为辅助手段来增强阿霉素对乳腺癌细胞的抗增殖作用。
