華東師范大學(xué)生科院生命醫(yī)學(xué)研究所劉明耀教授課題組最近在國(guó)際癌癥研究權(quán)威雜志《癌癥研究》第69期14卷上發(fā)表了一篇題為《11-羰基-β-乙酰乳香酸通過(guò)干擾血管內(nèi)皮生長(zhǎng)因子受體-2介導(dǎo)的血管新生效應(yīng),,抑制人前列腺腫瘤生長(zhǎng)》的學(xué)術(shù)論文,再一次揭示了植物藥單體化合物在抑制腫瘤生長(zhǎng)方面的巨大潛力,。
劉明耀教授率領(lǐng)的抗腫瘤血管生成和抗癌藥物篩選課題組已在《癌癥研究》上發(fā)表了一系列關(guān)于中草藥單體化合物抑制腫瘤生長(zhǎng)的學(xué)術(shù)論文,。最近,通過(guò)系統(tǒng)的實(shí)驗(yàn)研究,,劉明耀教授課題組發(fā)現(xiàn)11-羰基-β-乙酰乳香酸(縮寫為AKBA)在腫瘤血管新生中的重要作用及分子機(jī)理,。
基礎(chǔ)理論證明,當(dāng)實(shí)體腫瘤達(dá)到一定體積后(通常2~3mm3),,彌漫在其周圍組織中氧氣和養(yǎng)分無(wú)法滿足其進(jìn)一步生長(zhǎng),。此時(shí),腫瘤細(xì)胞會(huì)分泌多種細(xì)胞生長(zhǎng)因子,,促發(fā)在其周圍形成紊亂無(wú)序的,、不成熟的新生血管,為其提供“養(yǎng)料”,,即導(dǎo)致腫瘤血管新生,。
劉明耀教授課題組研究發(fā)現(xiàn),11-羰基-β-乙酰乳香酸通過(guò)干擾內(nèi)皮細(xì)胞生長(zhǎng)因子受體和雷帕霉素靶蛋白信號(hào)通路,,抑制血管內(nèi)皮細(xì)胞的增殖,、遷移以及小管狀結(jié)構(gòu)形成,從而阻斷新生血管形成,,降低腫瘤的營(yíng)養(yǎng)供應(yīng),,抑制前列腺癌的生長(zhǎng)。
據(jù)了解,,乳香酸是傳統(tǒng)中藥乳香的有效活性成分,,提取于卡氏乳香樹(shù)的橡膠脂中,而11-羰基-β-乙酰乳香酸是乳香酸的結(jié)構(gòu)衍生物,??ㄊ先橄銟?shù)廣泛分布于熱帶區(qū)域,在中國(guó)的海南省,、臺(tái)灣南部,、廣東南部、廣西南部及云南南部等地區(qū)都有種植,。
一直以來(lái),,乳香酸就被視為一種抗炎藥,用于治療關(guān)節(jié)炎、呼吸道感染等疾病,,該項(xiàng)科學(xué)研究揭示了乳香酸能有效控制腫瘤生長(zhǎng)這一嶄新的功能和機(jī)理,,提示了11-羰基-β-乙酰乳香酸這一類化合物有可能成為安全的、有效的抗腫瘤藥物,。(生物谷Bioon.com)
生物谷推薦原始出處:
Cancer Research 69, 5893, July 15, 2009.doi: 10.1158/0008-5472.CAN-09-0755
Acetyl-11-Keto-β-Boswellic Acid Inhibits Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2–Mediated Angiogenesis
Xiufeng Pang1,2, Zhengfang Yi1, Xiaoli Zhang1, Bokyung Sung3, Weijing Qu1, Xiaoyuan Lian1, Bharat B. Aggarwal3 and Mingyao Liu1,2
1 Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China and 2 Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center and 3 Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
The role of angiogenesis in tumor growth and metastasis is well established. Identification of a small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we showed that acetyl-11-keto-β-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBA) after solid tumors reached 100 mm3 (n = 5). The inhibitory effect of AKBA on tumor growth was well correlated with suppression of angiogenesis. When examined for the molecular mechanism, we found that AKBA significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively suppressed vascular endothelial growth factor (VEGF)–induced microvessel sprouting in rat aortic ring assay ex vivo. Furthermore, AKBA inhibited VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures from primary cultured human umbilical vascular endothelial cells in a dose-dependent manner. Western blot analysis and in vitro kinase assay revealed that AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2) kinase (KDR/Flk-1) with IC50 of 1.68 μmol/L. Specifically, AKBA suppressed the downstream protein kinases of VEGFR2, including Src family kinase, focal adhesion kinase, extracellular signal-related kinase, AKT, mammalian target of rapamycin, and ribosomal protein S6 kinase. Our findings suggest that AKBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signaling pathways.