Wasa Junji, Sugiura Hideshi, Kozawa Eiji, Kohyama Keishi, Yamada Kenji, Taguchi Osamu
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya. Japan.
Anticancer Res. 2011 Jan;31(1):123-7.
Angiogenesis is involved in the growth and metastasis of most solid tumors. Several reports have demonstrated that angiotensin II stimulates growth and migration of certain cancer cell lines and induces angiogenesis through up-regulation of vascular endothelial growth factor. This study examined whether an angiotensin II type 1 receptor (AT1R) antagonist (CV11974) inhibits osteosarcoma progression and distant metastasis.
Osteosarcoma (LM8) was transplanted into subcutaneous dorsal tissue of C3H mice. The mice were administered CV11974 daily by intraperitoneal injections at 0.1 mg/kg, 1 mg/kg, or 10 mg/kg, or saline for 28 days.
Subcutaneous tumor size was smaller in the CV11974 treatment groups than in the control group. Lung and liver metastases were significantly reduced in the CV11974 treatment groups when compared with the control group.
CV11974 is widely used to treat hypertension clinically and therefore may be a novel antiangiogenic therapy for osteosarcoma through blocking AT1R-mediated signaling.
血管生成参与大多数实体瘤的生长和转移。多项报告表明，血管紧张素II可刺激某些癌细胞系的生长和迁移，并通过上调血管内皮生长因子诱导血管生成。本研究检测血管紧张素II 1型受体（AT1R）拮抗剂（CV11974）是否能抑制骨肉瘤进展和远处转移。
将骨肉瘤（LM8）移植到C3H小鼠的背部皮下组织。通过腹腔注射，每天给予小鼠0.1 mg/kg、1 mg/kg或10 mg/kg的CV11974，或生理盐水，持续28天。
CV11974治疗组的皮下肿瘤大小比对照组小。与对照组相比，CV11974治疗组的肺和肝转移明显减少。
CV11974在临床上广泛用于治疗高血压，因此可能是一种通过阻断AT1R介导的信号传导来治疗骨肉瘤的新型抗血管生成疗法。
