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

Authors
Elmira Kalantari 1
Hajar Saeidi 1
Niloofar Shabani Kia 1
Zoya Tahergorabi 1
Bahman Rashidi 2
Nasim Dana 3
Majid Khazaei 1
1 Department of Physiology, Students Research Center, Faculty of Medicine, Isfahan, Iran
2 Department of Anatomy, Isfahan University of Medical Sciences, Isfahan, Iran
3 Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
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.

Keywords

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Advanced Biomedical Research
Volume 2013, November
November 2013
Pages 1-4