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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2013
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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 |
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author | Kalantari, Elmira Saeidi, Hajar Kia, Niloofar Shabani Tahergorabi, Zoya Rashidi, Bahman Dana, Nasim Khazaei, Majid |
author_facet | Kalantari, Elmira Saeidi, Hajar Kia, Niloofar Shabani Tahergorabi, Zoya Rashidi, Bahman Dana, Nasim Khazaei, Majid |
author_sort | Kalantari, Elmira |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3908495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-39084952014-02-11 Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice Kalantari, Elmira Saeidi, Hajar Kia, Niloofar Shabani Tahergorabi, Zoya Rashidi, Bahman Dana, Nasim Khazaei, Majid Adv Biomed Res Original Article 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. Medknow Publications & Media Pvt Ltd 2013-11-30 /pmc/articles/PMC3908495/ /pubmed/24520550 http://dx.doi.org/10.4103/2277-9175.122498 Text en Copyright: © 2013 Kalantari http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Original Article Kalantari, Elmira Saeidi, Hajar Kia, Niloofar Shabani Tahergorabi, Zoya Rashidi, Bahman Dana, Nasim Khazaei, Majid Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice |
title | Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice |
title_full | Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice |
title_fullStr | Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice |
title_full_unstemmed | Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice |
title_short | Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice |
title_sort | effect of dapt, a gamma secretase inhibitor, on tumor angiogenesis in control mice |
topic | Original Article |
url | 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 |
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