NK-18, a promising antimicrobial peptide: anti-multidrug resistant leukemia cells and LPS neutralizing properties.

NK-18, a promising antimicrobial peptide: anti-multidrug resistant leukemia cells and LPS neutralizing properties.
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NK-18,一种有前途的抗菌肽:抗多药耐药性白血病细胞和 LPS 中和特性。

DOI:
10.1016/j.biochi.2018.02.001
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发表时间:
2018-04
期刊:
影响因子:
3.9
通讯作者:
赵丽
赵丽
中科院分区:
生物学3区
文献类型:
--
作者:
闫洁熙;梁晓磊;赵丽

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随着多药耐药性的增加,需要具有不同作用机制的新型抗白血病药物来应对这一挑战。NK-18是哺乳动物源性蛋白NK-lysin的核心区域,可有效抑制多药耐药和敏感白血病细胞系的生存力。同时,对白血病敏感细胞株和多药耐药细胞株的增殖抑制作用不明显。NK-18在非致瘤细胞和致瘤细胞之间表现出选择性。它优先与磷脂酰丝氨酸含量高的肿瘤细胞结合。NK-18通过在细胞膜上迅速形成小孔作用于多药耐药白血病细胞株,K562/ADM细胞不易产生对NK-18的耐药性。NK-18还能通过静电引力中和脂多糖,减少NO的产生。这些研究数据表明,NK-18在治疗多药耐药白血病方面具有很大的优势,与传统的化疗相比,它可能是一个潜在的候选人进行进一步的研究。
With the increase of multidrug resistance, novel anti-leukemia agents with diverse mechanisms of action are required to address this challenge. NK-18, the core region of mammalian derived protein NK-lysin, effectively inhibited the viability of both multidrug resistant and sensitive leukemia cell lines. Meanwhile, this proliferation inhibition effect was not distinct between sensitive and multidrug resistant leukemia cell line. NK-18 showed selectivity between non-tumorigenic and tumorigenic cells. It preferentially bound to tumor cells whose outer leaflet with high phosphatidylserine content. NK-18 acted on the multidrug resistant leukemia cell line by a rapid pore formation on the cell membrane, it is not easy for K562/ADM cells developing resistance against NK-18. Furthermore, NK-18 could neutralize lipopolysaccharides by electrostatic attraction and reduce NO production. These research data demonstrated NK-18 possesses great advantage in the multidrug resistant leukemia treatment compared with conventional chemotherapies and it could be a potential candidate for further research.
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