Angiotensin II type 1 receptor antagonist suppress angiogenesis and growth of gastric cancer xenografts.
Angiotensin II (Ang II) has been reported to promote tumor progression, tumor growth and angiogenesis in many cancers. We previously observed that angiotensin II type 1 receptors (AT1R) were upregulated in human gastric cancer and may be involved in the progression of gastric cancer. We studied the effects of AT1R antagonist on angiogenesis and growth in gastric cancer xenografts to observe the mechanism action of AT1R in the gastric cancer. The results showed that the growth of gastric cancer cells was significantly suppressed by treatment with AT1R antagonist. In vivo, TCV-116, at doses of both 2 and 5 mg/kg/day, significantly suppressed tumor growth in mice (47.3 and 70.2%). Microvessel density was significantly decreased by TCV-116 (3.4 +/- 0.9 and 2.8 +/- 0.5 per field) compared with the control group (12.9 +/- 1.1 per field), and VEGF expression was significantly suppressed by AT1R antagonist. These results demonstrate that AT1R plays an important role in the progression of gastric cancer. Suppression tumor angiogenesis could be one of the mechanisms by which AT1R antagonist suppresses the growth of gastric cancer. These findings also provide a theoretical basis for the future clinical application of AT1R antagonist against gastric cancer.
Huang
Wei
W
Department of Gastroenterology, Ruijin Hospital, School of Medicine, Jiaotong University, Shanghai, China.
Wu
Yun-Lin
YL
Zhong
Jie
J
Jiang
Feng-Xiang
FX
Tian
Xiang-Long
XL
Yu
Li-Fen
LF
D000284:Administration, Oral; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; C077793:candesartan cilexetil