Angiotensin II type I antagonist prevents pulmonary metastasis of murine renal cancer by inhibiting tumor angiogenesis.
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.
Miyajima
Akira
A
Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan. akiram@ndmc.ac.jp
Kosaka
Takeo
T
Asano
Tomohiko
T
Asano
Takako
T
Seta
Kaori
K
Kawai
Toshiaki
T
Hayakawa
Masamichi
M
D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000096:biosynthesis; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C081643:candesartan