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首页> 外文期刊>Journal of cellular physiology. >15-LOX-1 has diverse roles in the resensitization of resistant cancer cell lines to doxorubicin
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15-LOX-1 has diverse roles in the resensitization of resistant cancer cell lines to doxorubicin

机译：resensitization 15-LOX-1有不同的角色阿霉素的抗肿瘤细胞系

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摘要

Lipoxygenases (LOXs) are a family of enzymes that can oxygenate polyunsaturated fatty acids. As a member of the family, 15-lipoxygenase-1 (15-LOX-l) specifically metabolizes arachidonic acid and linoleic acid. 15-LOX-l can affect physiological and pathophysio-logical events via regulation of the protein-lipid interactome, alterations in intracellular redox state and production of lipid metabolites that are involved in the induction and resolution of inflammation. Although several studies have shown that 15-LOX-1 has an antitumorigenic role in many different cancer models, including breast cancer, the role of the protein in cancer drug resistance has not been established yet. In this study, we, for the first time, aimed to show the potential role of 15-LOX-1 in acquired doxorubicin (DOX) resistance in MCF7 and HeLa cancer cell lines. Our results show that ALOX15 was transcriptionally downregulated in DOX-resistant cells compared with their drug-sensitive counterparts. Moreover, overexpression of ALOX15 in the drug-resistant cells resulted in resensitization of those cells to DOX in a cell-dependent manner. 15-LOX-1 expression could induce apoptosis by activating PPARy and enhance the accumulation of DOX in drug-resistant MCF7 cells by altering cellular motility properties, and membrane dynamics. However, HeLa DOX cells did not show any of these effects but were susceptible to cell death when treated with 13(S)-HODE. These results underline the role and importance of 15-LOX-1 in cancer drug resistance, and points to novel mechanisms as a therapeutic approach to overcome cancer drug resistance.
机译：脂氧合酶(lox)是酶的一个家庭可以充氧多不饱和脂肪酸。家庭成员,15-lipoxygenase-1(15-LOX-l)专门代谢花生四烯酸酸和亚油酸。通过生理和pathophysio-logical事件监管的protein-lipid interactome,细胞内氧化还原状态变化脂质代谢产物所涉及的生产感应和分辨率的炎症。尽管一些研究已经表明,15-LOX-1有抗癌的作用在许多不同的吗癌症模型,包括乳腺癌,这个角色的蛋白质在肿瘤耐药性被建立了。第一次,旨在展示的潜在作用15-LOX-1获得性耐阿霉素(阿霉素)在MCF7和海拉癌症细胞系。表明ALOX15转录表达下调DOX-resistant细胞进行比较与非同行。过度的ALOX15耐药这些细胞的细胞导致resensitization阿霉素在cell-dependent方式。表达可能通过激活诱导细胞死亡PPARy,增强阿霉素的积累通过改变细胞耐药MCF7细胞运动性属性和膜动力学。然而,海拉阿霉素的细胞没有表现出任何这些影响但时容易受到细胞死亡13 (S)蚯蚓处理。15-LOX-1癌症的作用和重要性耐药性,并指出小说机制作为一个克服癌症药物治疗方法阻力。

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