Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Sci Rep. 2024 Mar 9;14(1):5792. doi: 10.1038/s41598-024-56605-1.
Cisplatin is a chemotherapy drug widely used in cancer treatment. Alongside its clinical benefits, however, it may inflict intolerable toxicity and other adverse effects on healthy tissues. Due to the limitation of administering a high dose of cisplatin as well as cancer drug resistance, it is necessary to utilize new methods optimizing treatment modalities through both higher therapeutic efficacy and reduced administered doses of radiation and drugs. In this study, sensitive (A2780) and resistant (A2780CP) ovarian carcinoma cells underwent treatment with cisplatin + static magnetic field (SMF). First, the levels of genotoxicity after treatment were evaluated by Comet assay. Then, cell cycle analysis and apoptosis assay were conducted by a flow cytometer. Lastly, the expression levels of genes involved in apoptosis and cellular drug uptake were investigated by PCR. After treating different groups of cells for 24, 48, and 96 h, the co-treatment of SMF and cisplatin as a combination managed to increase the amount of DNA damage in both sensitive and resistant cell lines. A considerable increase in mortality of cells was also observed mostly in the form of apoptosis, which was caused by inhibition of the cell cycle. The combination also increased the expression levels of apoptotic genes, namely P53 and P21; however, it did not have much effect on the expression levels of BCL2. Besides, the levels of CTR1 gene expression increased significantly in the groups receiving the aforementioned combination. Our study suggests that the combination of cisplatin + SMF might have clinical potential which needs further investigations through future studies.
顺铂是一种广泛用于癌症治疗的化疗药物。然而,除了其临床益处外,它可能会对健康组织造成无法忍受的毒性和其他不良反应。由于限制给予高剂量顺铂以及癌症药物耐药性,因此有必要利用新的方法通过提高治疗效果和减少辐射和药物的给予剂量来优化治疗方式。在这项研究中,敏感(A2780)和耐药(A2780CP)卵巢癌细胞接受顺铂+静磁场(SMF)治疗。首先,通过彗星试验评估治疗后遗传毒性水平。然后,通过流式细胞仪进行细胞周期分析和凋亡分析。最后,通过 PCR 研究参与凋亡和细胞摄取药物的基因的表达水平。在对不同组的细胞进行 24、48 和 96 小时处理后,SMF 和顺铂的联合治疗成功地增加了敏感和耐药细胞系中 DNA 损伤的量。还观察到细胞死亡率的显著增加,主要以细胞凋亡的形式出现,这是由细胞周期抑制引起的。该联合还增加了凋亡基因(即 P53 和 P21)的表达水平;然而,它对 BCL2 的表达水平没有太大影响。此外,在接受上述联合治疗的组中,CTR1 基因表达水平显著增加。我们的研究表明,顺铂+SMF 的联合可能具有临床潜力,需要通过未来的研究进一步探讨。
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