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褪黑素增加骨肉瘤细胞对化疗药物顺铂的敏感性。

Melatonin Increases the Sensitivity of Osteosarcoma Cells to Chemotherapy Drug Cisplatin.

机构信息

Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Drug Res (Stuttg). 2022 Jul;72(6):312-318. doi: 10.1055/a-1830-8716. Epub 2022 May 30.

DOI:10.1055/a-1830-8716
PMID:35636434
Abstract

Chemotherapy, which is one of the common treatments for osteosarcoma (OS), has many side effects and in some cases has low effectiveness due to chemoresistance, hence it is vital to study new therapies for OS. In this regard, we combined melatonin with cisplatin and evaluate their effect on MG63 OS cells. Since melatonin has anti-cancer properties, we hypothesized that its combination with cisplatin could increase the effectiveness of cisplatin. Firstly, MTT assay was used to evaluate the cell viability and cytotoxicity of cisplatin on MG63 cells and the results showed that melatonin in combination with cisplatin increases the sensitivity of MG63 cells to cisplatin. In addition, qRT-PCR results showed that the expressions of miR-181 and P53, CYLD, CBX7 and BCL2 genes change in MG63 cells after treatment with the combination of cisplatin and melatonin, so that the expression of P53, CYLD and CBX7 increased and the expression of BCL2 and miR-181b decreases significantly. Furthermore, analysis of Annexin V/FITC assay data revealed that the rate of apoptosis in MG63 OS cell line remarkably promoted after treated with cisplatin and melatonin combination. As a result, our findings show that melatonin in combination with cisplatin increases the effectiveness of cisplatin in osteosarcoma cells and this study provides a new therapeutic approach for OS.

摘要

化疗是骨肉瘤(OS)的常见治疗方法之一,但由于化疗耐药性,其具有许多副作用,在某些情况下疗效较低,因此研究骨肉瘤的新疗法至关重要。在这方面,我们将褪黑素与顺铂联合使用,并评估它们对 MG63 骨肉瘤细胞的作用。由于褪黑素具有抗癌特性,我们假设其与顺铂联合使用可以提高顺铂的疗效。首先,通过 MTT 法评估顺铂对 MG63 细胞的细胞活力和细胞毒性,结果表明褪黑素与顺铂联合使用可提高 MG63 细胞对顺铂的敏感性。此外,qRT-PCR 结果显示,MG63 细胞经顺铂和褪黑素联合处理后,miR-181 和 P53、CYLD、CBX7 和 BCL2 基因的表达发生变化,使 P53、CYLD 和 CBX7 的表达增加,BCL2 和 miR-181b 的表达显著降低。此外,Annexin V/FITC 检测分析数据显示,MG63 OS 细胞系经顺铂和褪黑素联合处理后,细胞凋亡率显著提高。因此,我们的研究结果表明,褪黑素与顺铂联合使用可提高顺铂在骨肉瘤细胞中的疗效,为骨肉瘤的治疗提供了新的方法。

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