narasin的氧化应激诱导增强了阿霉素治疗骨肉瘤的疗效。

IF 2.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Zhaoming Han, Juguang Yang, Ping Wang, Feng Bian, Jiguang Jia
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引用次数: 0

摘要

化疗引起的并发症和脂肪毒性是骨肉瘤临床治疗的主要挑战。鉴定能够在较低剂量下增强化疗疗效的药物可能代表一种替代治疗策略。Narasin是一种广泛应用于兽医学的聚醚类抗生素。在这项研究中,我们发现narasin在对正常细胞毒性较小的相同浓度下对骨肉瘤细胞具有活性。这种作用是通过氧化应激和损伤以及线粒体功能障碍介导的生长抑制和细胞凋亡诱导来实现的。抗氧化剂N-乙酰基-1-半胱氨酸(NAC)消除了抗骨肉瘤的活性。重要的是,narasin显著增强了阿霉素在骨肉瘤细胞培养系统和皮下植入小鼠模型中的疗效。narasin和阿霉素在无毒剂量下的组合完全阻止了小鼠骨肉瘤的生长。我们的研究结果表明,同时给予阿霉素和纳拉辛可以为骨肉瘤提供一种可行的替代治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Oxidative stress induction by narasin augments doxorubicin's efficacy in osteosarcoma.

Complications and fata toxicity induced by chemotherapy are the main challenge for clinical management of osteosarcoma. The identification of agents that can augment the efficacy of chemotherapy at lower doses may represent an alternative therapeutic strategy. Narasin is a polyether antibiotic widely used in veterinary medicine. In this study, we show that narasin is active against osteosarcoma cells at the same concentrations that are less toxic to normal cells. This effect is achieved by growth inhibition and apoptosis induction, which is mediated by oxidative stress and damage, and mitochondrial dysfunction. The antioxidant N-acetyl-l-cysteine (NAC) abolishes the anti-osteosarcoma activity. Importantly, narasin significantly augments doxorubicin's efficacy in both osteosarcoma cell culturing system and subcutaneous implantation mouse model. The combination of narasin and doxorubicin at non-toxic doses completely arrests osteosarcoma growth in mice. Our results suggest that the concurrent administration of doxorubicin and narasin could present a viable alternative therapeutic approach for osteosarcoma.

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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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