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Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 3149
© 2004 American Society of Clinical Oncology
Effects of 5-fluorouracil on endothelial nitric oxide synthase in endothelial cells in different states of confluence
V. M. Casado-Echarren,
C. Abarrategui,
R. Alvarez,
G. Rubio,
A. León,
M. Dómine,
I. Calvo,
L. G. Estévez,
A. López-Farré and
F. Lobo
Fundacion Jimenez Diaz, Madrid, Spain
3149
Background: Some studies suggest a direct effect of 5-fluoruracil (5-FU) on vascular endothelium. The enzyme endothelial nitric-oxide synthase (eNOS) produces nitric oxide (NO) in the endothelium. It is known that NO has multiple physiological functions one of which is involved in the interaction of circulating tumour cells with the endothelium. On the other hand, endothelial cells (E.C) can be found in two different states of proliferation: confluence (quiescent) and subconfluence (proliferating). Our objetives are to study the effect of 5-FU on the eNOS expression and to analyse if there is a direct relationship between the effect of 5-FU and eNOs expression and the state of endothelial growth. Methods: Culture of bovine aortal endothelial cells (B.A.E.C). The dosage of 5-FU was 20 ugr/mL. The enzyme eNOS was measured using Western-blot method. Results: We observed an increase in eNOs expression in subconfluent E.C with respect to confluent E.C (14.6 densitometric units as opposed 8.97 DU;p<0.003; t Student method).The presence of 5-FU reduces eNOS expression in subconfluent E.C with respect to control subconfluent endothelial cells (14.6 DU as opposed to 9.47; p< 0.023). Conclusions: 5-FU reduces eNOs expression in E.C in subconfluence state. This finding suggests a direct effect of 5-FU on the proliferating endothelium and as well a possible effect on tumoral endothelium.
No significant financial relationships to disclose.
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