RRC ID 41580
著者 Fujita M, Hayashi I, Yamashina S, Itoman M, Majima M.
タイトル Blockade of angiotensin AT1a receptor signaling reduces tumor growth, angiogenesis, and metastasis.
ジャーナル Biochem Biophys Res Commun
Abstract It was reported that angiotensin II stimulates angiogenesis in vivo, and angiotensin-converting enzyme (ACE) inhibitors inhibit angiogenesis. We found that an AT1-receptor (AT1-R) antagonist, TCV-116, inhibited tumor growth, tumor-associated angiogenesis, and metastasis in a murine model. Tumor growth of Sarcoma 180 (S-180) cells and of fibrosarcoma (NFSA) cells was strongly inhibited by administration of TCV-116 in the diet at a dose of approximately 100 mg/kg/day. This reduction was accompanied with a marked reduction in tumor-associated angiogenesis. The same treatment also reduced the lung metastasis of intravenously injected Lewis lung carcinoma cells. These effects of TCV-116 were equivalent to those of the ACE inhibitor, lisinopril. In S-180 and NFSA tumor tissues, ACE and AT1a receptor (AT1a-R) mRNAs were expressed when assessed with RT-PCR. AT1b receptor and AT2 receptor, however, were not detected. Immunoreactive AT1-R was detected mainly on the neovascularized vascular endothelial cells in which expression was reduced by TCV-116 and lisinopril. These results suggested that TCV-116 inhibits the angiogenesis, growth, and metastasis of tumors highly dependent on AT1a-R blockade. Blockade of AT1a-R signaling may therefore become an effective novel strategy for tumor chemoprevention.
巻・号 294(2)
ページ 441-7
公開日 2002-6-7
DOI 10.1016/S0006-291X(02)00496-5
PII S0006-291X(02)00496-5
PMID 12051731
MeSH Angiotensin Receptor Antagonists* Animals Antihypertensive Agents / pharmacology Antineoplastic Agents / pharmacology Benzimidazoles / pharmacology* Biphenyl Compounds / pharmacology* Carcinoma, Lewis Lung / drug therapy* Carcinoma, Lewis Lung / metabolism Carcinoma, Lewis Lung / pathology Cell Division / drug effects Drug Screening Assays, Antitumor Fibrosarcoma / drug therapy* Fibrosarcoma / metabolism Fibrosarcoma / pathology Immunohistochemistry Lisinopril / pharmacology Male Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred ICR Neoplasm Metastasis / prevention & control Neoplasm Transplantation Neovascularization, Pathologic / prevention & control Peptidyl-Dipeptidase A / biosynthesis Peptidyl-Dipeptidase A / genetics RNA, Messenger / biosynthesis Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Receptors, Angiotensin / biosynthesis Receptors, Angiotensin / genetics Sarcoma 180 / drug therapy Sarcoma 180 / metabolism Sarcoma 180 / pathology Sarcoma, Experimental / drug therapy* Sarcoma, Experimental / metabolism Sarcoma, Experimental / pathology Signal Transduction / drug effects* Tetrazoles*
IF 2.985
引用数 180
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 NFSa Y83(RCB0282)