Formation of blood vessels is a fundamental element in the control of tumour growth in which vascular endothelial growth factor (VEGF) and nitric oxide (NO) have been demonstrated to be involved. Our aim was to analyse whether changes in the expression of endothelial NO synthase (eNOS) and VEGF in colonic tissue could be detected early and even before the identification of colon tumour-associated morphological modifications in azoxymethane-treated rats. We studied further whether aspirin treatment changed these parameters. An increased expression of both eNOS and VEGF in colonic tissue from azoxymethane-treated rats compared with that from control rats was found. Aspirin treatment (10 mg/kg of body weight per day) reduced eNOS expression, but failed to modify the expression of VEGF in the colonic tissue of azoxymethane-treated rats. No evidence of aberrant crypt formation or changes in the number of blood vessels were observed in the colon of any of the animals studied. Expression of the VEGF receptor Flk-1, but not Flt-1, was increased in colonic tissue of azoxymethane-treated rats compared with control rats. The expression of Flk-1 was mainly localized in the epithelial cells, particularly in the lower part of the crypt. Aspirin treatment reduced Flk-1 expression in both control and azoxymethane-treated rats. Caspase-3 activity, which has been considered as an apoptotic index, was almost undetectable in azoxymethane-treated rats. Aspirin treatment stimulated caspase-3 activity. Overexpression of eNOS, VEGF and its receptor Flk-1 occurred early after azoxymethane administration in rat colonic tissue, even before morphological changes associated with tumour generation were observed, and aspirin prevented the overexpression of both eNOS and VEGF receptor Flk-1.
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Research Article|
January 01 2004
Aspirin inhibits endothelial nitric oxide synthase (eNOS) and Flk-1 (vascular endothelial growth factor receptor-2) prior to rat colon tumour development
Marta ESCRIBANO;
Marta ESCRIBANO
*Digestive Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Laura MOLERO;
Laura MOLERO
†Cardiovascular Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Antonio LÓPEZ-FARRÉ;
Antonio LÓPEZ-FARRÉ
†Cardiovascular Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Cynthia ABARRATEGUI;
Cynthia ABARRATEGUI
*Digestive Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Carolina CARRASCO;
Carolina CARRASCO
†Cardiovascular Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Antonio GARCÍA-MENDEZ;
Antonio GARCÍA-MENDEZ
*Digestive Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Félix MANZARBEITIA;
Félix MANZARBEITIA
‡Department of Anatomopathology, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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María Jesús MARTÍN;
María Jesús MARTÍN
*Digestive Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Marian VÁZQUEZ;
Marian VÁZQUEZ
*Digestive Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Paloma SÁNCHEZ-FAYOS;
Paloma SÁNCHEZ-FAYOS
*Digestive Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Luis RICO;
Luis RICO
†Cardiovascular Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
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Juan Carlos PORRES CUBERO
*Digestive Research Laboratory, Fundación Jiménez Díaz, Av. Reyes Católicos 2, 28040 Madrid, Spain
Correspondence: Dr Juan Carlos Porres Cubero (e-mail blarrea@fjd.es).
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Publisher: Portland Press Ltd
Received:
May 30 2003
Revision Received:
July 25 2003
Accepted:
August 27 2003
Accepted Manuscript online:
August 27 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2004 The Biochemical Society
2004
Clin Sci (Lond) (2004) 106 (1): 83–91.
Article history
Received:
May 30 2003
Revision Received:
July 25 2003
Accepted:
August 27 2003
Accepted Manuscript online:
August 27 2003
Citation
Marta ESCRIBANO, Laura MOLERO, Antonio LÓPEZ-FARRÉ, Cynthia ABARRATEGUI, Carolina CARRASCO, Antonio GARCÍA-MENDEZ, Félix MANZARBEITIA, María Jesús MARTÍN, Marian VÁZQUEZ, Paloma SÁNCHEZ-FAYOS, Luis RICO, Juan Carlos PORRES CUBERO; Aspirin inhibits endothelial nitric oxide synthase (eNOS) and Flk-1 (vascular endothelial growth factor receptor-2) prior to rat colon tumour development. Clin Sci (Lond) 1 January 2004; 106 (1): 83–91. doi: https://doi.org/10.1042/CS20030192
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