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Angiotensin II Type I Antagonist Prevents Pulmonary Metastasis of Murine Renal Cancer by Inhibiting Tumor Angiogenesis

Departments of Urology [A. M., T. K., To. A., Ta. A., K. S., M. H.] and Pathology [T. K.], National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan

Angiotensin II (AII) is a potent vasoconstrictor peptide from the renin-angiotensin system in the kidney. The AII type 1 receptor (AT1R) is reportedly expressed in several tumors including renal cell carcinoma, and AII is involved in tumor angiogenesis. We p.o. administered the long-acting AT1R antagonist, candesartan (10 mg/kg), to the 16 days mouse renal cancer lung metastasis model to test the preventive effects in tumor metastasis. Pulmonary metastases of renal cancer showed prominent AT1R expression in both mice and humans, and candesartan treatment dramatically prevented lung metastatic nodules (14.9 ± 1.8; P < 0.0001; n = 12) in mice along with the inhibition of neovascularization and vascular endothelial growth factor expression, compared with control metastatic mice (123.3 ± 8.6; n = 13). Candesartan is widely used clinically, so it seems to be a reasonable therapy for patients with lung metastases of renal cell carcinoma.

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