Department of Dental Pharmacology, School of Dentistry, and Brain Korea 21 project, Chonbuk National University, Jeon-Ju, Chonbuk561-756, Republic of Korea.
Eur J Pharmacol. 2012 Sep 15;691(1-3):28-37. doi: 10.1016/j.ejphar.2012.06.028. Epub 2012 Jul 1.
Hypoxia-inducible factor-1 (HIF-1) consists of two subunits, the HIF-1β, which is constitutively expressed, and HIF-1α, which is oxygen-responsive. HIF-1α is over-expressed in response to hypoxia, increasing transcriptional activity linked to tumor progression, angiogenesis, metastasis, and invasion. This study aimed to demonstrate that the natural compound, Bavachinin, has potent anti-angiogenic activity in vitro and in vivo. Bavachinin inhibited increases in HIF-1α activity in human KB carcinoma (HeLa cell derivative) and human HOS osteosarcoma cells under hypoxia in a concentration-dependent manner, probably by enhancing the interaction between von Hippel-Lindau (VHL) and HIF-1α. Furthermore, Bavachinin decreased transcription of genes associated with angiogenesis and energy metabolism that are regulated by HIF-1, such as vascular endothelial growth factors (VEGF), Glut 1 and Hexokinase 2. Bavachinin also inhibited tube formation in human umbilical vein endothelial cells (HUVECs) as well as in vitro migration of KB cells. In vivo studies showed that injecting Bavachinin thrice weekly for four weeks significantly reduced tumor volume and CD31 expression in nude mice with KB xenografts. These data indicate that Bavachinin could be used as a therapeutic agent for inhibiting tumor angiogenesis.
缺氧诱导因子-1（HIF-1）由两个亚基组成，HIF-1β是组成型表达的，HIF-1α是对氧响应的。HIF-1α在缺氧时过度表达，增加与肿瘤进展、血管生成、转移和侵袭相关的转录活性。本研究旨在证明天然化合物巴维辛具有体外和体内的强大抗血管生成活性。巴维辛以浓度依赖的方式抑制缺氧下人 KB 癌（HeLa 细胞系）和人 HOS 骨肉瘤细胞中 HIF-1α活性的增加，可能是通过增强 von Hippel-Lindau（VHL）和 HIF-1α之间的相互作用。此外，巴维辛还降低了由 HIF-1 调节的与血管生成和能量代谢相关的基因的转录，如血管内皮生长因子（VEGF）、Glut 1 和己糖激酶 2。巴维辛还抑制了人脐静脉内皮细胞（HUVEC）中的管形成以及 KB 细胞的体外迁移。体内研究表明，每周注射三次巴维辛四周可显著减少裸鼠 KB 异种移植物的肿瘤体积和 CD31 表达。这些数据表明，巴维辛可作为抑制肿瘤血管生成的治疗剂。
