Background
Leptomycin B (LMB) is an inhibitor of chromosome region maintenance 1 (CRM1) that is one of the nuclear protein exporters[1]. The IC50 value of Leptomycin B is 0.1-10 nM. Leptomycin B has a potent anti-tumor, anti-inflammatory and neuroprotective effects[2-3].
10-100 nM Leptomycin B(0-100 nM; 48 h) significantly reduced the viability of HGC-27 cells[4]. Leptomycin B (0.5nM; 48 h) displayed a synergistic effect on gefitinib-induced cytotoxicity in A549 cells[5].
Leptomycin B(30 mg/ml(100μl); i.c.v; 7days) prevents status epilepticus (SE) -induced vasogenic edema formation accompanied by preservation of blood-brain barrier (BBB) integrity[6]. Leptomycin B(10 μg/mL (20 μM), 1 μg/mL (2 μM), 100 ng/mL (200 nM), or 10 ng/ mL (20 nM)) can effectively inhibit the inflammatory response and the expression of matrix metalloproteinase (MMP)-9 after UV-B irradiation in mice skin[7].
参考文献:
[1]. Scaffidi P, Misteli T, et,al. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002 Jul 11;418(6894):191-5. doi: 10.1038/nature00858. Erratum in: Nature. 2010 Sep 30;467(7315):622. PMID: 12110890.
[2]. Lu C, Shao C, et,al. Chemotherapeutic sensitization of leptomycin B resistant lung cancer cells by pretreatment with doxorubicin. PLoS One. 2012;7(3):e32895. doi: 10.1371/journal.pone.0032895. Epub 2012 Mar 7. PMID: 22412944; PMCID: PMC3296751.
[3]. Loewe R, Holnthoner W, et,al. Dimethylfumarate inhibits TNF-induced nuclear entry of NF-kappa B/p65 in human endothelial cells. J Immunol. 2002 May 1;168(9):4781-7. doi: 10.4049/jimmunol.168.9.4781. PMID: 11971029.
[4]. Zhu H, Yang Y, et,al. Leptomycin B inhibits the proliferation, migration, and invasion of cultured gastric carcinoma cells. Biosci Biotechnol Biochem. 2020 Feb;84(2):290-296. doi: 10.1080/09168451.2019.1673148. Epub 2019 Oct 16. PMID: 31619134.
[5]. Liu Z, Gao W. Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21. PMID: 28942004; PMCID: PMC5643250.
[6]. Kim DS, Min SJ, et,al. Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway. Brain Res. 2016 Nov 15;1651:27-35. doi: 10.1016/j.brainres.2016.09.023. Epub 2016 Sep 19. PMID: 27659963.
[7]. Kobayashi T, Shinkai H. Leptomycin B reduces matrix metalloproteinase-9 expression and suppresses cutaneous inflammation. J Invest Dermatol. 2005 Feb;124(2):331-7. doi: 10.1111/j.0022-202X.2004.23595.x. PMID: 15675951.
Leptomycin B (LMB)是染色体区域维持1 (CRM1)的抑制剂,CRM1是核蛋白输出蛋白之一[1]。Leptomycin B的IC50值为0.1 ~ 10 nM。Leptomycin B具有有效的抗肿瘤、抗炎和神经保护作用[2-3]。
10 ~ 100 nM Leptomycin B(0-100 nM; 48 h)显著降低HGC-27细胞活力[4]。Leptomycin B (0.5nM; 48 h)对吉非替尼Gefitinib诱导的A549细胞毒性具有协同作用[5]。
Leptomycin B(30 mg/ml(100μl); i.c.v; 7days)可以防止癫痫持续状态(SE)诱导的血管源性水肿形成,同时保持血脑屏障(BBB)的完整性[6]。Leptomycin B(10 μg/mL (20 μM), 1 μg/mL (2 μM), 100 ng/mL (200 nM), or 10 ng/ mL (20 nM))能有效抑制UV-B照射后小鼠皮肤的炎症反应和基质金属蛋白酶(MMP)-9的表达[7]。
Protocol
| Cell experiment [1]: |
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Cell lines
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HGC-27 cells
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Preparation Method
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Cells were incubated with 0, 1, 10, or 100 nM of leptomycin B for 48 h.
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Reaction Conditions
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0-100 nM; 48 h
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Applications
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10-100 nM Leptomycin B significantly reduced the viability of HGC-27 cells.
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| Animal experiment [2]: |
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Animal models
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Male Sprague-Dawley (SD) rats (7 weeks old)
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Preparation Method
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Mice were anesthetized and placed in a stereotaxic frame. A brain infusion kit was implanted into the right lateral ventricle (1 mm posterior; 1.5 mm lateral; 3.5 mm depth to the bregma) and connected to an osmotic pump (1007D) containing: (1) vehicle; (2) LMB (30 mg/ml). The mice were induced to have epileptic reactions after intracerebroventricular drug infusion.
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Dosage form
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30 mg/ml(100μl); i.c.v; 7days
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Applications
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Leptomycin B prevents status epilepticus (SE) -induced vasogenic edema formation accompanied by preservation of blood-brain barrier (BBB) integrity.
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参考文献:
[1]. Zhu H, Yang Y,et,al. Leptomycin B inhibits the proliferation, migration, and invasion of cultured gastric carcinoma cells. Biosci Biotechnol Biochem. 2020 Feb;84(2):290-296. doi: 10.1080/09168451.2019.1673148. Epub 2019 Oct 16. PMID: 31619134.
[2]. Kim DS, Min SJ, et,al. Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway. Brain Res. 2016 Nov 15;1651:27-35. doi: 10.1016/j.brainres.2016.09.023. Epub 2016 Sep 19. PMID: 27659963.
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