藤黄是我国一种传统中草药，我国古代医书中曾记载“藤黄性毒而能攻毒”，现代医学研究为这一说法找到了证据。
经过多年研究，华东师范大学生命医学研究所刘明耀教授带领的课题组发现，从藤黄属植物中提取的一种植物药单体“藤黄双黄酮”，可抑制肿瘤血管的生成和肿瘤生长，相关论文已发表在国际癌症权威杂志《癌症研究》上。
肿瘤血管是肿瘤生长、侵润和转移的“帮凶”。在肿瘤形成的早期，瘤体并无血管生长，主要靠氧气和营养物质的弥散来维持生存，肿瘤也仅能长到2立方毫米—3立方毫米。但一旦有新生的血管与其相连，肿瘤就能源源不断地通过“血流灌注”方式，获得营养物质补给，就会以几何级数迅速生长，同时肿瘤细胞还可以通过新生血管转移到其他器官。
因此，抑制肿瘤血管的生成就可以切断肿瘤的营养来源、“饿死”肿瘤。这种“血管新生治疗法”目前已成为肿瘤国际研究的前沿领域。
刘明耀教授课题组研究发现，“藤黄双黄酮”能通过调控细胞胞外的激酶信号通路和小G蛋白活力，来抑制人脐静脉内皮细胞的增殖、迁移以及小管状结构形成，从而阻断血管新生，切断肿瘤的营养供应，进而抑制肿瘤生长。
业内专家认为，这一研究表明“藤黄双黄酮”这一类化合物有可能成为安全有效的抗肿瘤新药。目前，国内外市场上抗血管生成药物价格昂贵，一般病人无法承受，而藤黄在我国分布广泛，具有广阔的市场开发前景。
目前，华东师范大学生命医学研究所已经成立了抗血管生成药物筛选中心，从我国丰富的中药资源中筛选安全、有效、机体可以承受的以及靶点机制明确的肿瘤血管生成抑制剂。课题组现已发现多种植物药单体具有抗血管生成活性，并申请了多项专利。新药开发的进一步基础研究也正在进行中。（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer Research 69, 518, January 15, 2009. doi: 10.1158/0008-5472.CAN-08-2531
Morelloflavone, a Biflavonoid, Inhibits Tumor Angiogenesis by Targeting Rho GTPases and Extracellular Signal-Regulated Kinase Signaling Pathways
Xiufeng Pang1,2, Tingfang Yi2, Zhengfang Yi1, Sung Gook Cho2, Weijing Qu1, Decha Pinkaew4, Ken Fujise3 and Mingyao Liu1,2
1 Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; 2 Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Houston, Texas; 3 Division of Cardiology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; and 4 Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla, Thailand
Morelloflavone, a biflavonoid extracted from Garcinia dulcis, has shown antioxidative, antiviral, and anti-inflammatory properties. However, the function and the mechanism of this compound in cancer treatment and tumor angiogenesis have not been elucidated to date. In this study, we postulated that morelloflavone might have the ability to inhibit angiogenesis, the pivotal step in tumor growth, invasiveness, and metastasis. We showed that morelloflavone could inhibit vascular endothelial growth factor (VEGF)–induced cell proliferation, migration, invasion, and capillary-like tube formation of primary cultured human umbilical vascular endothelial cells in a dose-dependent manner. Morelloflavone effectively inhibited microvessel sprouting of endothelial cells in the mouse aortic ring assay and the formation of new blood microvessels induced by VEGF in the mouse Matrigel plug assay. Furthermore, morelloflavone inhibited tumor growth and tumor angiogenesis of prostate cancer cells (PC-3) in xenograft mouse tumor model in vivo, suggesting that morelloflavone inhibited tumorigenesis by targeting angiogenesis. To understand the underlying mechanism of morelloflavone on the inhibitory effect of tumor growth and angiogenesis, we showed that morelloflavone could inhibit the activation of both RhoA and Rac1 GTPases but have little effect on the activation of Cdc42 GTPase. Additionally, morelloflavone inhibited the phosphorylation and activation of Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase/ERK pathway kinases without affecting VEGF receptor 2 activity. Together, our results indicate that morelloflavone exerts antiangiogenic action by targeting the activation of Rho-GTPases and ERK signaling pathways. These findings are the first to reveal the novel functions of morelloflavone in tumor angiogenesis and its molecular basis for the anticancer action.
