Open AccessEffect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice
Author(s) -
Elmira Kalantari,
Hajar Saeidi,
Niloofar Shabani Kia,
Zoya Tahergorabi,
Bahman Rashidi,
Nasim Dana,
Majid Khazaei
Publication year - 2013
Publication title -
advanced biomedical research
Language(s) - English
Resource type - Journals
ISSN - 2277-9175
DOI - 10.4103/2277-9175.122498
Subject(s) - angiogenesis , cd31 , medicine , vascular endothelial growth factor , neovascularization , angiogenesis inhibitor , notch signaling pathway , nitric oxide , endocrinology , immunohistochemistry , blood vessel , receptor , pharmacology , cancer research , vegf receptors
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