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) |