RESUMO
Glioma is the most common type of malignant intracranial tumor in adults and is associated with the highest mortality rate. Although surgery, radiotherapy, chemotherapy and other treatment methods have progressed, the median survival of patients with glioma is only 1415 months. Glioma cells are able to penetrate along blood vessels and invade into the surrounding normal brain tissue so that an overall resection of the tumor cannot be performed. In the process of metastasis, the resistance of cancer cells to anoikis has an important role. When tumor cells escape from their original environment, anoikis resistance aids their survival. In the present study, reverse transcriptionsemiquantitative polymerase chain reaction (RTsqPCR), RTquantitative PCR and western blotting demonstrated that the transcription factor, motor neuron and pancreas homeobox 1 (MNX1), was ectopically expressed in glioma cells compared with normal HUVECC human umbilical vein endothelial cells. Furthermore, its expression was higher in more malignant glioma cell lines (T98G and M059K) compared with the less malignant glioma cell line (U87 MG) and normal HUVECC cells. An adhesion assay using fibronectin demonstrated that MNX1 and tyrosine kinase receptor B (TrkB) overexpression in HUVECC and U87 MG cells reduced adhesion and forced them to suspend. Additionally, MNX1 and TrkB overexpression was demonstrated to increase the ability of cells to bypass anoikis. MNX1 and TrkB knockdown increased adhesion and promoted apoptosis after suspension. It was further demonstrated that MNX1 functioned as a transcription factor binding in the upstream regulatory region of TrkB to activate its expression. The results of the present study suggested that MNX1 may suppress the adhesion and apoptosis rates of tumor cells by activating TrkB. The results of the present study suggest that MNX1 may represent a novel therapeutic target for the treatment of gliomas.
Assuntos
Anoikis/genética , Glioma/genética , Glioma/metabolismo , Proteínas de Homeodomínio/genética , Receptor trkB/metabolismo , Fatores de Transcrição/genética , Sítios de Ligação , Adesão Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioma/patologia , Proteínas de Homeodomínio/metabolismo , Humanos , Neurônios Motores/metabolismo , Motivos de Nucleotídeos , Ligação Proteica , Receptor trkB/genética , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
PURPOSE: To demonstrate the relationship between of sphingosine-1-phosphate (S1P) expression and subarachnoid hemorrhage (SAH). METHODS: The basilar arteries from a "double-hemorrhage" rabbit model of SAH were used to investigate the relation between S1P expression and SAH. Various symptoms, including blood clots, basilar artery cross-sectional area, and S1P phosphatase expression were measured at day 3, 5, 7, 9. RESULTS: The expression of S1P was enhanced in the cerebral vasospasm after subarachnoid hemorrhage in the rabbits. And S1P expression was consistent with the basilar artery cross-sectional area changes at day 3, 5, 7, 9. CONCLUSION: Sphingosine-1-phosphate expression in the cerebral arterial may be a new indicator in the development of cerebral vasospasm after subarachnoid hemorrhage and provide a new therapeutic method for SAH.
Assuntos
Lisofosfolipídeos/análise , Esfingosina/análogos & derivados , Hemorragia Subaracnóidea/patologia , Vasoespasmo Intracraniano/patologia , Animais , Artéria Basilar/patologia , Modelos Animais de Doenças , Citometria de Fluxo , Coelhos , Distribuição Aleatória , Esfingosina/análise , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/metabolismo , Fatores de Tempo , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/metabolismoRESUMO
PURPOSE:To demonstrate the relationship between of sphingosine-1-phosphate (S1P) expression and subarachnoid hemorrhage (SAH).METHODS:The basilar arteries from a "double-hemorrhage" rabbit model of SAH were used to investigate the relation between S1P expression and SAH. Various symptoms, including blood clots, basilar artery cross-sectional area, and S1P phosphatase expression were measured at day 3, 5, 7, 9.RESULTS: The expression of S1P was enhanced in the cerebral vasospasm after subarachnoid hemorrhage in the rabbits. And S1P expression was consistent with the basilar artery cross-sectional area changes at day 3, 5, 7, 9.CONCLUSION: Sphingosine-1-phosphate expression in the cerebral arterial may be a new indicator in the development of cerebral vasospasm after subarachnoid hemorrhage and provide a new therapeutic method for SAH.