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虾青素降低阿糖胞苷对急性淋巴细胞白血病细胞系 NALM-6 的生长抑制剂量和炎症反应。

Astaxanthin decreases the growth-inhibitory dose of cytarabine and inflammatory response in the acute lymphoblastic leukemia cell line NALM-6.

机构信息

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

Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.

出版信息

Mol Biol Rep. 2022 Jul;49(7):6415-6422. doi: 10.1007/s11033-022-07452-8. Epub 2022 Apr 20.

Abstract

BACKGROUND

In spite of the great progress in acute lymphoblastic leukemia (ALL) treatment, a large number of patients still suffer from chemotherapy drug toxicity. As a routine medication for ALL treatment, cytarabine (Ara-C) has many side effects on the patients. Astaxanthin (ASX), on the other hand, is a carotenoid with antioxidant, anti-inflammatory and anti-cancer properties.

PURPOSE

The present study investigated the effects of ASX in combination with Ara-C on cell proliferation, apoptosis induction, and cell cycle arrest in NALM-6 cell line.

METHODS

NALM6 cells were treated with different concentrations of ASX, Ara-C, and their co-treatment. Cytotoxic effects were evaluated using MTT assay. After treating the cells with the IC50 dose of ASX, Ara-C and their co-treatment, we studied apoptosis induction, cell cycle arrest, and expression of apoptotic, anti-apoptotic, and inflammatory genes.

RESULT

MTT assay demonstrated that co-treatment of cytarabine and ASX had greater cytotoxicity effects compared with the IC50 dose of Ara-C alone. After 48 h of treatment of NALM-6 cells with the combination dose, expression levels of apoptotic genes (P53, caspase-8, 3), the anti-apoptotic gene (Bcl-xL) and inflammatory genes (IL-6, TNF-α) changed significantly compared to the untreated group (p < 0.05).

CONCLUSIONS

Co-treatment of ASX and Ara-C has synergism effects on apoptosis pathways, cell proliferation inhibition, and decreased inflammation.

摘要

背景

尽管急性淋巴细胞白血病(ALL)的治疗取得了巨大进展,但仍有大量患者遭受化疗药物毒性的影响。阿糖胞苷(Ara-C)作为 ALL 治疗的常规药物,对患者有许多副作用。虾青素(ASX)是一种具有抗氧化、抗炎和抗癌特性的类胡萝卜素。

目的

本研究旨在探讨 ASX 联合 Ara-C 对 NALM-6 细胞系增殖、凋亡诱导和细胞周期阻滞的影响。

方法

用不同浓度的 ASX、Ara-C 及其联合处理 NALM6 细胞,MTT 法评估细胞毒性。用 ASX、Ara-C 和其联合处理的 IC50 剂量处理细胞后,研究凋亡诱导、细胞周期阻滞和凋亡、抗凋亡及炎症基因的表达。

结果

MTT 法表明,与单独使用 Ara-C 的 IC50 剂量相比,阿糖胞苷和 ASX 的联合处理具有更大的细胞毒性作用。用联合剂量处理 NALM-6 细胞 48 小时后,与未处理组相比,凋亡基因(P53、caspase-8、3)、抗凋亡基因(Bcl-xL)和炎症基因(IL-6、TNF-α)的表达水平显著变化(p<0.05)。

结论

ASX 和 Ara-C 的联合治疗对凋亡途径、细胞增殖抑制和炎症减少具有协同作用。

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