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葡萄糖通过降低铁存在下 ω-3 多不饱和脂肪酸的抗氧化特性增加慢性髓性白血病的增殖和化疗耐药性。

Glucose increases proliferation and chemoresistance in chronic myeloid leukemia via decreasing antioxidant Properties of ω-3 polyunsaturated fatty acids in the presence of Iron.

机构信息

Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.

Department of Physiology, School of Allied Medical Sciences, Birjand University of Medical Sciences, Birjand, Iran.

出版信息

Mol Biol Rep. 2023 Dec;50(12):10315-10324. doi: 10.1007/s11033-023-08891-7. Epub 2023 Nov 16.

Abstract

BACKGROUND

There is a strong association between hyperglycemia, oxidative stress, inflammation and the onset and progression of diabetes which causes a higher risk of cancer. This study investigated, the effect of concomitant use of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) with iron supplements in hyper-glucose conditions on the K-562 cell line.

METHODS

The effects of iron, ω-3 PUFAs, and a combination of both on K-562 cells were investigated under normal and high glucose conditions. The impact of these treatments was evaluated using multiple methodologies, including the MTT assay for cell viability, quantification of oxidative stress markers [total antioxidant capacity (TAC) and malondialdehyde (MDA)], and analysis of the cell cycle. Furthermore, the expression levels of TNFα and p53 mRNA were measured using Real-time PCR.

RESULTS

The co-treatment of ω-3 PUFAs and iron in the presence of high glucose had notable effects, as evidenced by an increase in cell survival, resistance to imatinib chemotherapy, TNFαmRNA expression levels, MDA levels, and percentage of cells in the G2/S phase. Additionally, there was a decrease in the mRNA expression of p53 and TAC levels compared to treatment in the normal-glucose condition.

CONCLUSION

Hyperglycemic conditions in conjunction with the combined treatment of theω-3 PUFAs and iron, led to reduced anticancer capacity, chemosensitivity, anti-inflammatory and antioxidant properties of the K-562 cells. These effects were found to be mediated by oxidative stress.

摘要

背景

高血糖、氧化应激、炎症与糖尿病的发生和进展密切相关,这会增加癌症的风险。本研究旨在探讨在高葡萄糖条件下,同时使用ω-3 多不饱和脂肪酸(ω-3 PUFAs)和铁补充剂对 K-562 细胞系的影响。

方法

在正常和高葡萄糖条件下,研究了铁、ω-3 PUFAs 以及两者联合对 K-562 细胞的影响。使用多种方法评估这些处理的影响,包括 MTT 法测定细胞活力、氧化应激标志物[总抗氧化能力(TAC)和丙二醛(MDA)]的定量分析以及细胞周期分析。此外,使用 Real-time PCR 测定 TNFα和 p53 mRNA 的表达水平。

结果

高葡萄糖存在下ω-3 PUFAs 和铁的联合治疗具有显著影响,表现为细胞存活率增加、对伊马替尼化疗的耐药性增加、TNFαmRNA 表达水平增加、MDA 水平增加以及 G2/S 期细胞比例增加。此外,与正常葡萄糖条件下的治疗相比,p53 mRNA 表达和 TAC 水平降低。

结论

高血糖条件与ω-3 PUFAs 和铁的联合治疗共同作用,导致 K-562 细胞的抗癌能力、化疗敏感性、抗炎和抗氧化特性降低。这些作用是通过氧化应激介导的。

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