Abstract：
OBJECTIVE: 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.
METHODS: 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 G2 arrest were confirmed by a western blot assay and confocal microscopy.
RESULTS: 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 G2 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).
CONCLUSIONS: These findings support the use of PEMF stimulation as an adjuvant to strengthen the antiproliferative effect of doxorubicin on breast cancer cells.
METHODS: 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 G2 arrest were confirmed by a western blot assay and confocal microscopy.
RESULTS: 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 G2 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).
CONCLUSIONS: These findings support the use of PEMF stimulation as an adjuvant to strengthen the antiproliferative effect of doxorubicin on breast cancer cells.
摘要：
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各种类型癌症的抗癌药物，包括乳腺癌.然而,PEMF刺激对多柔比星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刺激对阿霉素在人乳腺癌MDA-MB-231细胞中抗癌活性的影响。
方法：将MDA-MB-231细胞接种并孵育48小时。用阿霉素处理细胞，顺铂,5-氟尿嘧啶,或紫杉醇48小时。随后，每天三次（每次间隔4小时）用60分钟的PEMF疗程刺激细胞，持续24或48小时。通过锥虫蓝染料排除试验评估细胞活力，并通过流式细胞术分析细胞周期分析。通过蛋白质印迹分析和共聚焦显微镜证实了G2晚期停滞的分子机制。
结果:用多柔比星和PEMF的组合处理的MDA-MB-231细胞具有显著低于单独用多柔比星处理的细胞的活力。PEMF刺激通过增强髓鞘转录因子1（MYT1）表达来抑制细胞周期蛋白依赖性激酶1（CDK1）活性，从而在G2后期增加阿霉素诱导的细胞周期停滞，细胞分裂周期25C（CDC25C）磷酸化，和分层(14-3-3σ)表达式。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。
结论：这些发现支持使用PEMF刺激作为佐剂来增强多柔比星对乳腺癌细胞的抗增殖作用。
方法：将MDA-MB-231细胞接种并孵育48小时。用阿霉素处理细胞，顺铂,5-氟尿嘧啶,或紫杉醇48小时。随后，每天三次（每次间隔4小时）用60分钟的PEMF疗程刺激细胞，持续24或48小时。通过锥虫蓝染料排除试验评估细胞活力，并通过流式细胞术分析细胞周期分析。通过蛋白质印迹分析和共聚焦显微镜证实了G2晚期停滞的分子机制。
结果:用多柔比星和PEMF的组合处理的MDA-MB-231细胞具有显著低于单独用多柔比星处理的细胞的活力。PEMF刺激通过增强髓鞘转录因子1（MYT1）表达来抑制细胞周期蛋白依赖性激酶1（CDK1）活性，从而在G2后期增加阿霉素诱导的细胞周期停滞，细胞分裂周期25C（CDC25C）磷酸化，和分层(14-3-3σ)表达式。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。
结论：这些发现支持使用PEMF刺激作为佐剂来增强多柔比星对乳腺癌细胞的抗增殖作用。
