The Key Laboratory, The First Hospital of Lanzhou University, Lanzhou, 730000, China.
High Altitude Medical Research Center, School of Medicine, Tibet University, Lhasa, 850000, China.
Biochimie. 2018 Apr;147:143-152. doi: 10.1016/j.biochi.2018.02.001. Epub 2018 Feb 7.
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.
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 是哺乳动物来源蛋白 NK-细胞溶素的核心区域,能有效抑制多药耐药和敏感白血病细胞系的活力。同时,这种增殖抑制作用在敏感和多药耐药白血病细胞系之间没有明显区别。NK-18 在非致瘤细胞和致瘤细胞之间具有选择性。它优先结合外叶磷脂酰丝氨酸含量高的肿瘤细胞。NK-18 通过在细胞膜上快速形成孔来作用于多药耐药白血病细胞系,K562/ADM 细胞不易对 NK-18 产生耐药性。此外,NK-18 可以通过静电吸引中和脂多糖并减少 NO 的产生。这些研究数据表明,与传统化疗相比,NK-18 在治疗多药耐药白血病方面具有很大优势,可能成为进一步研究的潜在候选药物。