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Cancer Chemother Pharmacol. 2010 May;66(1):79-87. doi: 10.1007/s00280-009-1136-0. Epub 2009 Sep 22.

Inhibition of angiotensin II receptor 1 limits tumor-associated angiogenesis and attenuates growth of murine melanoma.

Author information

1
Laboratório de Oncologia Experimental (LIM-24), Departamento de Radiologia e Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo, 455 room 4112/4122, São Paulo, Brazil.

Abstract

PURPOSE:

We evaluated the involvement of angiotensin II (AngII)-dependent pathways in melanoma growth, through the pharmacological blockage of AT1 receptor by the anti-hypertensive drug losartan (LOS).

RESULTS:

We showed immunolabeling for both AngII and the AT1 receptor within the human melanoma microenvironment. Like human melanomas, we showed that murine melanomas also express the AT1 receptor. Growth of murine melanoma, both locally and at distant sites, was limited in mice treated with LOS. The reduction in tumor growth was accompanied by a twofold decrease in tumor-associated microvessel density and by a decrease in CD31 mRNA levels. While no differences were found in the VEGF expression levels in tumors from treated animals, reduction in the expression of the VEGFR1 (Flt-1) at the mRNA and protein levels was observed. We also showed downregulation of mRNA levels of both Flt-4 and its ligand, VEGF-C.

CONCLUSIONS:

Together, these results show that blockage of AT1 receptor signaling may be a promising anti-tumor strategy, interfering with angiogenesis by decreasing the expression of angiogenic factor receptors.

PMID:
19771429
DOI:
10.1007/s00280-009-1136-0
[Indexed for MEDLINE]

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