Manmuan Suwisit, Sakunrangsit Nithidol, Ketchart Wannarasmi
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Clin Exp Pharmacol Physiol. 2017 Oct;44(10):1042-1052. doi: 10.1111/1440-1681.12806. Epub 2017 Aug 24.
Salinomycin is a monocarboxylic polyether ionophore isolated from Streptomyces albus. It has been widely used as an antibiotic in veterinary medicine in poultry. A recent study demonstrated that salinomycin selectively inhibits human breast cancer stem cells; one possible mechanism of tamoxifen resistance. Our results show that salinomycin is effective in inhibiting MCF-7/LCC2 and MCF-7/LCC9 cell lines which are well-established endocrine resistant cells and has a synergistic effect in combination with tamoxifen using MTT proliferation assay. The inhibitory effect of salinomycin on the reduction of critical ER co-activator; amplified breast 1 (AIB1) mRNA and protein expression is overcoming tamoxifen resistance. Moreover, salinomycin significantly inhibits cell invasion in Matrigel invasion assay. The effect was mediated at least in part by the decrease of matrix metalopeptidase 9 (MMP-9) which is one critical enzyme facilitated in the cell invasion process. In conclusion, salinomycin should be developed as a novel agent used alone or in combination for endocrine-resistant breast cancer.
盐霉素是一种从白色链霉菌中分离出的单羧酸聚醚离子载体。它在兽医学中作为家禽用抗生素被广泛使用。最近一项研究表明，盐霉素可选择性抑制人乳腺癌干细胞；这是他莫昔芬耐药的一种可能机制。我们的结果显示，盐霉素对MCF-7/LCC2和MCF-7/LCC9细胞系有效，这两种细胞系是公认的内分泌耐药细胞，并且使用MTT增殖试验表明盐霉素与他莫昔芬联合使用具有协同作用。盐霉素对关键雌激素受体共激活因子——扩增的乳腺癌1（AIB1）mRNA和蛋白表达降低的抑制作用正在克服他莫昔芬耐药。此外，在基质胶侵袭试验中盐霉素显著抑制细胞侵袭。该作用至少部分是由基质金属肽酶9（MMP-9）的减少介导的，MMP-9是细胞侵袭过程中一种关键酶。总之，盐霉素应被开发为一种单独使用或联合使用的新型药物，用于治疗内分泌耐药性乳腺癌。
