抗菌肽对抗肿瘤细胞的机制：选择性膜破坏和非膜溶解

Antineoplastic mechanism of antimicrobial peptides: selective membrane destruction and non-membrane dissolution

背景:抗菌肽作为一种可从自然中提取并且对快速增殖的细胞产生毒性的宿主免疫基本成分,引起了科学家们广泛关注。熟悉抗菌肽的抗肿瘤机制才能更好的将其应用于临床实践中。目的:综述近年来抗菌肽抗肿瘤机制的研究进展。方法:由第一作者应用计算机检索Pub Med、Springerlink、Web of Science、Science Direct等数据库2015年1月至2019年5月发表的文献,检索词为"antimicrobial,peptide,antitumor mechanisms,antitumor activity,anti-neoplastic",选择与抗菌肽抗肿瘤机制及其研究进展相关的文献。结果与结论:核糖体合成的阳离子抗菌肽或宿主防御肽通过与细菌表面带负电荷脂质的静电相互作用显示出了广谱抗菌活性。与正常细胞相比,由于癌细胞表面的磷脂酰丝氨酸(带负电荷)比例增加,因此阳离子双亲肽可能是抗肿瘤药物的一个有效治疗方法,并且具有高选择性。抗菌肽的抗肿瘤机制从作用模式上可以分为2类:选择性膜破坏和非膜溶解作用机制,其代表性的抗肿瘤肽包括α防御素1、乳铁蛋白B等。抗菌肽抗肿瘤的临床应用主要制约在其稳定性及给药途径,通过对其进行结构优化,开发创新配方和药物输送系统,使这些抗菌肽在未来肿瘤治疗过程中发挥更大的作用。

BACKGROUND:Antimicrobial peptides,an extract from nature,are a basic component of host immunity that make toxic effect on highly proliferative cells.They have attracted extensive attention of scientists.The understanding of the antineoplastic mechanism of antimicrobial peptides can contribute to its application in clinical practice.OBJECTIVE:To summarize the research advances in antineoplastic mechanism of antimicrobial peptides.METHODS:The first author conducted a computer-based retrieval of Pub Med,Springerlink,Web of Science,and Science Direct databases for relevant articles published from January 2015 to May 2019.The keywords were"antimicrobial,peptide,antitumor mechanisms,antitumor activity and anti-neoplastic".The articles concerning antineoplastic mechanism of antimicrobial peptides and research progress were selected.RESULTS AND CONCLUSION:Cationic antimicrobial peptides synthesized by ribosomes and the host defense peptides can interac t with the membrane of bacteria,which showed a broad-spectrum antimicrobial activity.Compared with normal cells,the proportion of phosphatidylserine on the surface of cancer cells,which is negatively charged,is increased dramatically.As a result,the c ationic amphiphilic peptides are good candidate for the antineoplastic drugs,and possess a high selectivity.There are two major antitumor mechanism of antimicrobial peptides,which are selective membrane destruction and non-membrane dissolution(α-defensin-1 and lactoferrin B).The clinical application of antimicrobial peptides against tumors is mainly restricted by their stability and the ways to administration.By optimizing its structure and drug delivery systems,these antimicrobial peptides will play a critical role in the cancer treatment.