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Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice

BACKGROUND: Notch signaling is a key factor for angiogenesis in physiological and pathological condition and γ-secretase is the regulator of Notch signaling. The main goal of this study was to assess the effect of (N-[N-(3,5-Diflurophenaacetyl-L-alanyl)]-S-phenylglycine t-Butyl Ester) DAPT, a γ-secr...

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Detalles Bibliográficos
Autores principales: Kalantari, Elmira, Saeidi, Hajar, Kia, Niloofar Shabani, Tahergorabi, Zoya, Rashidi, Bahman, Dana, Nasim, Khazaei, Majid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908495/
https://www.ncbi.nlm.nih.gov/pubmed/24520550
http://dx.doi.org/10.4103/2277-9175.122498
Descripción
Sumario:BACKGROUND: Notch signaling is a key factor for angiogenesis in physiological and pathological condition and γ-secretase is the regulator of Notch signaling. The main goal of this study was to assess the effect of (N-[N-(3,5-Diflurophenaacetyl-L-alanyl)]-S-phenylglycine t-Butyl Ester) DAPT, a γ-secretase inhibitor, on serum angiogenic biomarkers, and tumor angiogenesis in control mice. MATERIALS AND METHODS: Tumor was induced by inoculation of colon adenocarcinoma cells (CT26) in 12 male Balb/C mice. When tumors size is reached to a 350 ± 50 mm(3), the animals were randomly divided into two groups: control and DAPT (n = 6/group). DAPT was injected subcutaneously 10 mg/kg/day. After 14 days, blood samples were taken and the tumors were harvested for immunohistochemical staining. RESULTS: Administration of DAPT significantly increased serum nitric oxide concentration and reduced vascular endothelial growth factor receptors-1 (VEGFR1) concentration without changes on serum VEGF concentration. DAPT reduced tumor vascular density in control mice (280.6 ± 81 vs. 386 ± 59.9 CD31 positive cells/mm(2)), although, it was not statistically significant. CONCLUSION: It seems that γ-secretase inhibitors can be considered for treatment of disorders with abnormal angiogenesis such as tumor angiogenesis.