Rajabi Fatemeh, Hajipour-Verdom Behnam, Abdolmaleki Parviz
Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154, Tehran, Iran.
Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, Academic Center for Education, Culture and Research (ACECR), 1517964311, Tehran, Iran.
Sci Rep. 2025 Apr 7;15(1):11902. doi: 10.1038/s41598-025-96802-0.
Osteosarcoma, a highly aggressive bone cancer, primarily affects adolescents and is frequently treated with conventional chemotherapy, such as doxorubicin (DOX). However, the efficacy of DOX is often limited by severe side effects and drug resistance. This study investigates the synergistic effects of static magnetic fields (SMF) and DOX on G292 osteosarcoma cells and HFF normal fibroblasts. Cell viability was assessed using the MTT assay, intracellular reactive oxygen species (ROS) levels were quantified via DCFDA staining and flow cytometry, and iron and calcium homeostasis were analyzed using ICP-OES. Apoptosis and necrosis were determined through Annexin V-FITC/PI staining. Results demonstrated that the combination of SMF and DOX significantly reduced G292 cell viability compared to DOX alone, with IC50 values decreased from 3.2 µM (at 3 mT, p < 0.01) to 0.8 µM (at 24 mT, p < 0.001) at 24 h. Apoptosis rates increased from 8.12% with DOX alone to 16% with SMF + DOX. While DOX alone elevated ROS levels by 59.15% in G292 cells, SMF further amplified apoptosis by enhancing ROS generation and disrupting iron and calcium homeostasis. These findings suggest that SMF enhances DOX-induced cytotoxicity in osteosarcoma cells by promoting ROS production, altering metal ion homeostasis, and increasing apoptosis. SMF represents a promising adjuvant therapy for osteosarcoma treatment, though further in vivo studies are necessary to optimize treatment parameters and evaluate clinical applicability.
骨肉瘤是一种侵袭性很强的骨癌,主要影响青少年,通常采用常规化疗进行治疗,如使用阿霉素(DOX)。然而,DOX的疗效常常受到严重副作用和耐药性的限制。本研究调查了静磁场(SMF)和DOX对G292骨肉瘤细胞和HFF正常成纤维细胞的协同作用。使用MTT法评估细胞活力,通过DCFDA染色和流式细胞术对细胞内活性氧(ROS)水平进行定量,并使用电感耦合等离子体发射光谱法(ICP - OES)分析铁和钙的稳态。通过Annexin V - FITC/PI染色确定凋亡和坏死情况。结果表明,与单独使用DOX相比,SMF和DOX联合使用显著降低了G292细胞的活力,在24小时时,IC50值从3.2 μM(在3 mT时,p < 0.01)降至0.8 μM(在24 mT时,p < 0.001)。凋亡率从单独使用DOX时的8.12%增加到SMF + DOX时的16%。虽然单独使用DOX可使G292细胞中的ROS水平升高59.15%,但SMF通过增强ROS生成以及破坏铁和钙的稳态进一步放大了凋亡。这些发现表明,SMF通过促进ROS产生、改变金属离子稳态和增加凋亡来增强DOX对骨肉瘤细胞的细胞毒性。SMF是骨肉瘤治疗中一种有前景的辅助治疗方法,不过还需要进一步的体内研究来优化治疗参数并评估临床适用性。