Lipoamide Inhibits NF1 Deficiency-induced Epithelial-Mesenchymal Transition in Murine Schwann Cells.
Arch Med Res
; 48(6): 498-505, 2017 08.
Article
en En
| MEDLINE
| ID: mdl-29198560
ABSTRACT
BACKGROUND AND AIMS:
Neurofibromatosis type I (NF1) is one of the most common neurocutaneous syndromes characterized by development of adult neurofibromas which is mainly made up of Schwann cells. The disease is generally accepted to be caused by inactivation mutation of Nf1 gene. And Nf1 deficiency had been reported to lead to ROS overproduction and epithelial-mesenchymal transition (EMT) phenotype. This study was designed to investigate whether excessive ROS conferred to Nf1 deficiency-induced EMT in Schwann cells.METHODS:
Colony formation, wound healing assay and transwell assay was used to evaluate the effects of stable Nf1 knockdown in SW10 Schwann cells. Western blot and ROS assay was conducted to explore the molecular mechanisms of Nf1 inactivation in tumorigenesis. Animal experiments were performed to assess the inhibitory effects of lipoamide, which is the neutral amide of α-lipoic acid and functions as a potent antioxidant to scavenge ROS, on Nf1-deficiency tumor growth in vivo.RESULTS:
Nf1 knockdown enhanced the cellular capacities of proliferation, migration and invasion, promoted ROS generation, decreased the expression of epithelial surface marker E-cadherin, and up-regulated several EMT-associated molecules in Schwann cells. Moreover, lipoamide dose-dependently inhibited not only Nf1 deficiency-induced EMT but also spontaneous EMT. Furthermore, lipoamide markedly suppresses tumor growth in a mouse model of NF1-associated neurofibroma.CONCLUSIONS:
Our results clearly reveal that ROS overproduction is responsible for Nf1 deficiency-induced EMT and plays a crucial role in NF1 tumor growth. The findings presented herein shed light on the potential of antioxidant therapy to prevent the progression of NF1-associated neurofibroma.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Células de Schwann
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Ácido Tióctico
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Genes de Neurofibromatosis 1
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Neurofibromatosis 1
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Especies Reactivas de Oxígeno
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Neurofibromina 1
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Transición Epitelial-Mesenquimal
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Neurofibroma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Arch Med Res
Asunto de la revista:
MEDICINA
Año:
2017
Tipo del documento:
Article
País de afiliación:
China