Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Integrative Oncology, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Sci Rep. 2023 Jul 5;13(1):10845. doi: 10.1038/s41598-023-38021-z.
The average survival of patients with glioblastoma is 12-15 months. Therefore, finding a new treatment method is important, especially in cases that show resistance to treatment. Extremely low-frequency electromagnetic fields (ELF-EMF) have characteristics and capabilities that can be proposed as a new cancer treatment method with low side effects. This research examines the antitumor effect of ELF-EMF on U87 and U251 glioblastoma cell lines. Flowcytometry determined the viability/apoptosis and distribution of cells in different phases of the cell cycle. The size of cells was assessed by TEM. Important cell cycle regulation genes mRNA expression levels were investigated by real-time PCR. ELF-EMF induced apoptosis in U87cells much more than U251 (15% against 2.43%) and increased G2/M cell population in U87 (2.56%, p value < 0.05), and S phase in U251 (2.4%) (data are normalized to their sham exposure). The size of U87 cells increased significantly after ELF-EMF exposure (overexpressing P53 in U251 cells increased the apoptosis induction by ELF-EMF). The expression level of P53, P21, and MDM2 increased and CCNB1 decreased in U87. Among the studied genes, MCM6 expression decreased in U251. Increasing expression of P53, P21 and decreasing CCNB1, induction of cell G2/M cycle arrest, and consequently increase in the cell size can be suggested as one of the main mechanisms of apoptosis induction by ELF-EMF; furthermore, our results demonstrate the possible footprint of P53 in the apoptosis induction by ELF-EMF, as U87 carry the wild type of P53 and U251 has the mutated form of this gene.
胶质母细胞瘤患者的平均存活时间为 12-15 个月。因此，寻找新的治疗方法很重要，尤其是在对治疗产生耐药的情况下。极低频率电磁场（ELF-EMF）具有可以作为副作用低的新癌症治疗方法的特征和能力。本研究检查了 ELF-EMF 对 U87 和 U251 胶质母细胞瘤细胞系的抗肿瘤作用。流式细胞术确定了细胞活力/凋亡和细胞在细胞周期不同阶段的分布。通过 TEM 评估细胞大小。通过实时 PCR 研究了重要的细胞周期调节基因 mRNA 表达水平。ELF-EMF 在 U87 细胞中诱导的细胞凋亡比 U251 多得多（15%对 2.43%），并增加了 U87 的 G2/M 细胞群（2.56%，p 值<0.05），并增加了 U251 的 S 期（2.4%）（数据相对于其假暴露进行归一化）。ELF-EMF 暴露后 U87 细胞的大小明显增加（U251 细胞中 P53 的过表达增加了 ELF-EMF 诱导的细胞凋亡）。U87 中 P53、P21 和 MDM2 的表达水平增加，CCNB1 减少。在所研究的基因中，U251 中的 MCM6 表达减少。P53、P21 表达增加和 CCNB1 减少，诱导细胞 G2/M 周期阻滞，进而细胞大小增加，可作为 ELF-EMF 诱导细胞凋亡的主要机制之一；此外，我们的结果表明 P53 可能在 ELF-EMF 诱导的细胞凋亡中起作用，因为 U87 携带 P53 的野生型，而 U251 具有该基因的突变形式。
