Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.
Environ Toxicol. 2014 Apr;29(4):363-70. doi: 10.1002/tox.21763. Epub 2012 Feb 13.
Hypoxia, a hallmark of many solid tumors, is associated with angiogenesis and tumor progression. Hypoxia-inducible factor-1 (HIF-1) plays a significant role in tumor angiogenesis. In this study, the authors constructed a selective platform to screen the traditional Chinese medicine as anti-angiogenic agent. The authors examined the molecular mechanism by which Scutellaria barbata regulates HIF-1-dependent expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor. Hypoxia promotes angiogenesis by increasing VEGF expression and secretion. Herein, the expression of VEGF was decreased by treatment with S. barbata in tumor cells. Meanwhile, S. barbata reduced the migration and proliferation of endothelial cells under hypoxic condition. S. barbata inhibited the expression of HIF-1α, as well as phosphorylated their upstream signal mediators AKT. S. barbata significantly inhibited the tumor growth in vivo and immunohistochemical studies in the tumors revealed decreased intratumoral microvessel density. These results suggest that the traditional Chinese medicine therapy using S. barbata, which exerts anti-angiogenic activities, represents a promising strategy for the treatment of tumors.
缺氧是许多实体瘤的一个标志，与血管生成和肿瘤进展有关。缺氧诱导因子-1（HIF-1）在肿瘤血管生成中起重要作用。在这项研究中，作者构建了一个选择性平台来筛选作为抗血管生成剂的中药。作者研究了半枝莲调节血管内皮生长因子（VEGF）的 HIF-1 依赖性表达的分子机制，VEGF 是一种重要的血管生成因子。缺氧通过增加 VEGF 的表达和分泌促进血管生成。在此，用半枝莲处理肿瘤细胞可降低 VEGF 的表达。同时，半枝莲减少了低氧条件下内皮细胞的迁移和增殖。半枝莲抑制了 HIF-1α的表达，并抑制了其上游信号介质 AKT 的磷酸化。半枝莲在体内显著抑制肿瘤生长，肿瘤组织的免疫组织化学研究显示肿瘤内微血管密度降低。这些结果表明，使用半枝莲的中药治疗具有抗血管生成活性，是治疗肿瘤的一种有前途的策略。
