藤黃是我國(guó)一種傳統(tǒng)中草藥,，我國(guó)古代醫(yī)書(shū)中曾記載“藤黃性毒而能攻毒”，現(xiàn)代醫(yī)學(xué)研究為這一說(shuō)法找到了證據(jù),。
經(jīng)過(guò)多年研究,，華東師范大學(xué)生命醫(yī)學(xué)研究所劉明耀教授帶領(lǐng)的課題組發(fā)現(xiàn)，從藤黃屬植物中提取的一種植物藥單體“藤黃雙黃酮”,，可抑制腫瘤血管的生成和腫瘤生長(zhǎng),，相關(guān)論文已發(fā)表在國(guó)際癌癥權(quán)威雜志《癌癥研究》上,。
腫瘤血管是腫瘤生長(zhǎng)、侵潤(rùn)和轉(zhuǎn)移的“幫兇”,。在腫瘤形成的早期,，瘤體并無(wú)血管生長(zhǎng)，主要靠氧氣和營(yíng)養(yǎng)物質(zhì)的彌散來(lái)維持生存,，腫瘤也僅能長(zhǎng)到2立方毫米—3立方毫米,。但一旦有新生的血管與其相連，腫瘤就能源源不斷地通過(guò)“血流灌注”方式,，獲得營(yíng)養(yǎng)物質(zhì)補(bǔ)給,，就會(huì)以幾何級(jí)數(shù)迅速生長(zhǎng)，同時(shí)腫瘤細(xì)胞還可以通過(guò)新生血管轉(zhuǎn)移到其他器官,。
因此,，抑制腫瘤血管的生成就可以切斷腫瘤的營(yíng)養(yǎng)來(lái)源、“餓死”腫瘤,。這種“血管新生治療法”目前已成為腫瘤國(guó)際研究的前沿領(lǐng)域,。
劉明耀教授課題組研究發(fā)現(xiàn)，“藤黃雙黃酮”能通過(guò)調(diào)控細(xì)胞胞外的激酶信號(hào)通路和小G蛋白活力,，來(lái)抑制人臍靜脈內(nèi)皮細(xì)胞的增殖、遷移以及小管狀結(jié)構(gòu)形成,，從而阻斷血管新生,，切斷腫瘤的營(yíng)養(yǎng)供應(yīng)，進(jìn)而抑制腫瘤生長(zhǎng),。
業(yè)內(nèi)專(zhuān)家認(rèn)為,，這一研究表明“藤黃雙黃酮”這一類(lèi)化合物有可能成為安全有效的抗腫瘤新藥。目前,，國(guó)內(nèi)外市場(chǎng)上抗血管生成藥物價(jià)格昂貴,，一般病人無(wú)法承受，而藤黃在我國(guó)分布廣泛,，具有廣闊的市場(chǎng)開(kāi)發(fā)前景,。
目前，華東師范大學(xué)生命醫(yī)學(xué)研究所已經(jīng)成立了抗血管生成藥物篩選中心,，從我國(guó)豐富的中藥資源中篩選安全,、有效、機(jī)體可以承受的以及靶點(diǎn)機(jī)制明確的腫瘤血管生成抑制劑,。課題組現(xiàn)已發(fā)現(xiàn)多種植物藥單體具有抗血管生成活性,，并申請(qǐng)了多項(xiàng)專(zhuān)利。新藥開(kāi)發(fā)的進(jìn)一步基礎(chǔ)研究也正在進(jìn)行中,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
