Cyclosporin A

Cyclosporin A（环孢素A）是一种选择性的亲环素（cyclophilin）抑制剂，IC50值为7 nM[1]。

亲环素是异构酶，参与各种与细胞代谢和能量平衡相关的功能。据报道，亲环素在炎症或恶性肿瘤中过表达。

Cyclosporin A是一种有效的亲环素抑制剂，负责MPTP（线粒体通透性转换孔）的开放。在视网膜神经节细胞中，cyclosporin A对亲环素D的表达具有高选择性，延长细胞存活[2]。在人早期妊娠滋养细胞中，cyclosporin A通过抑制Ca2+/钙调磷酸酶/NFAT信号，从而促进细胞生长和侵袭[3]。Cyclosporin A通过上调Fas/FasL和caspase活性，从而促进T细胞凋亡[4]。在人T细胞中，cyclosporin A通过抑制钙调磷酸酶和NFATc（负责T细胞的功能），从而抑制T细胞活化[1]。据报道，cyclosporin A通过干扰NTCP受体，从而抑制乙型和丙型肝炎病毒的进入[5]。在CRC细胞系（CACO-2、HT-29、HCT-116和LOVO）中，cyclosporin A也可通过非钙调磷酸酶途径影响细胞生长，同时钙调磷酸酶途径也被破坏[6]。

在视网膜缺血的C57BL/6小鼠模型中，cyclosporin A显著阻止亲环素D的上调，改善神经细胞的死亡[2]。

参考文献：
[1].  Minguillon, J., et al., Concentrations of cyclosporin A and FK506 that inhibit IL-2 induction in human T cells do not affect TGF-beta1 biosynthesis, whereas higher doses of cyclosporin A trigger apoptosis and release of preformed TGF-beta1. J Leukoc Biol, 2005. 77(5): p. 748-58.
[2].  Kim, S.Y., et al., Inhibition of cyclophilin D by cyclosporin A promotes retinal ganglion cell survival by preventing mitochondrial alteration in ischemic injury. Cell Death Dis, 2014. 5: p. e1105.
[3].  Du, M.R., et al., Cyclosporin A promotes growth and invasiveness in vitro of human first-trimester trophoblast cells via MAPK3/MAPK1-mediated AP1 and Ca2+/calcineurin/NFAT signaling pathways. Biol Reprod, 2008. 78(6): p. 1102-10.
[4].  Gao, J., et al., Mitochondrial permeability transition pore in inflammatory apoptosis of human conjunctival epithelial cells and T cells: effect of cyclosporin A. Invest Ophthalmol Vis Sci, 2013. 54(7): p. 4717-33.
[5].  Nkongolo, S., et al., Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin-independent interference with the NTCP receptor. J Hepatol, 2014. 60(4): p. 723-31.
[6].  Werneck, M.B., et al., Cyclosporin A inhibits colon cancer cell growth independently of the calcineurin pathway. Cell Cycle, 2012. 11(21): p. 3997-4008.