盐霉素抗肿瘤作用及其衍生物研究进展

肿瘤细胞中离子稳态的改变是影响肿瘤起始与进展的重要原因,为此人们将离子载体作为抗肿瘤药物进行研发。盐霉素是一种聚醚类离子载体抗生素,能够与钾离子、钠离子以非共价形式结合,协助离子跨膜转运,因而被用于防治鸡球虫病和促进反刍动物生长。新近研究发现,盐霉素具有杀伤多种肿瘤细胞尤其是特异杀伤肿瘤干细胞的作用,其可通过干预离子稳态、抑制肿瘤细胞相关信号通路和直接抑制其结合靶蛋白等发挥抗肿瘤作用,是潜在的新型抗肿瘤药物。然而,水溶性低、健康组织毒性、血液循环时间短等特点,限制了盐霉素的临床应用。新型衍生物或其靶向传递系统的开发,可有效提高盐霉素抗肿瘤作用及其安全性。现将盐霉素抗肿瘤应用、机制及其新药研究进展进行综述。

Research progress of salinomycin in suppressing tumor and its derivatives

Alterations of ion homeostasis palys an important role in tumor initiation and progression．For this reason,ionophores has been developed as potential anti-tumor drugs．Salinomycin is a polyether ionophore antibiotic,which can bind to potassium ions and sodium ions in a non-covalent manner,and assist ion transporting across the plasma membrane．For a long time,salinomycin has been used to prevent chicken coccidiosis and to promote ruminant growth．Recent studies have found that salinomycin has a role in killing a variety of tumor cells,especially cancer stem cells．Salinomycin kills cancer cells via interfering with ion homeostasis,inhibiting cancer cell signaling pathway and inhibiting its directly binding protein．Thus,salinomycin is a potential new anti-tumor drug．However,due to its toxic effects which including low solubility in water,toxicity to healthy tissues,short blood circulation and non-specific bio-distribution etc．,the further clinical application of salinomycin is limited．The development of new derivatives or targeting delivery systems would effectively improve the anti-tumor effect and safety profiles of salinomycin．This reviews summarized the research progress of salinomycin in suppressing tumor and its new drug development.