Gamma-secretase inhibitor does not modulate angiogenesis in colon adenocarcinoma in obese mice

Khazaei, M. and Kalantari, E. and Saeidi, H. and ShabaniKia, N. and Tahergorabi, Z. and Rashidi, B. and Dana, N. and Javanmard, S. H. (2015) Gamma-secretase inhibitor does not modulate angiogenesis in colon adenocarcinoma in obese mice. Bratislava Medical Journal, 116 (4). pp. 248-251.

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Abstract

Background: Notch is a signaling molecule which plays a role in angiogenesis and γ-secretase is required for processing of Notch. In this study, we investigated the effect of γ-secretase inhibitor (DAPT) on tumor angiogenesis in diet-induced obese mice. Methods: 18 mice were divided into three groups; control, obese (diet-induced) and obese+DAPT. After 15 weeks, the obese mice were subjected for tumor induction of CT26 colon adenocarcinoma cells (5 x 105 cells). When the tumor size reached approximately 350 ± 50 mm3, half of the obese animals received DAPT (10mg/kg/day) subcutaneously. Blood samples were taken after 14 days and the tumors harvested for immunohistochemical staining and capillary density were reported as CD31 positive cells/mm2. Results: The obese animals had higher serum leptin and NO concentrations, while, serum VEGF and VEGFR-1 concentrations were not different compare to control group. Administration of DAPT in obese mice significantly reduced serum VEGFR-1 and leptin concentrations and increased serum NO level (p < 0.05). Capillary density in the tumors of obese animals was not different compare to control groups. DAPT administration could not alter capillary density in the tumors. Conclusion: Administration of DAPT in obese mice altered serum angiogenic factors, however, it could not modulate tumor angiogenesis in diet-induced obese mice (Fig. 4, Ref. 26). Text in PDF www.elis.sk.

Item Type: Article
Additional Information: Cited By :3 Export Date: 16 February 2020 Correspondence Address: Khazaei, M.; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Azadi square, Iran
Uncontrolled Keywords: Adenocarcinoma Angiogenesis Obese γ-secretase amyloid precursor protein secretases dipeptides N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester animals antagonists and inhibitors Colonic Neoplasms complication Immunohistochemistry Male metabolism Mice Mice, Obese Neoplasms, Experimental Neovascularization, Pathologic Obesity pathology
Subjects: WI Digestive System
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib5 lib5
Date Deposited: 06 May 2020 08:40
Last Modified: 06 May 2020 08:40
URI: http://eprints.mums.ac.ir/id/eprint/18924

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