华东师范大学生科院生命医学研究所刘明耀教授课题组最近在国际癌症研究权威杂志《癌症研究》第69期14卷上发表了一篇题为《11－羰基－β－乙酰乳香酸通过干扰血管内皮生长因子受体－2介导的血管新生效应，抑制人前列腺肿瘤生长》的学术论文，再一次揭示了植物药单体化合物在抑制肿瘤生长方面的巨大潜力。
刘明耀教授率领的抗肿瘤血管生成和抗癌药物筛选课题组已在《癌症研究》上发表了一系列关于中草药单体化合物抑制肿瘤生长的学术论文。最近，通过系统的实验研究，刘明耀教授课题组发现11－羰基－β－乙酰乳香酸（缩写为AKBA）在肿瘤血管新生中的重要作用及分子机理。
基础理论证明，当实体肿瘤达到一定体积后（通常2～3mm3），弥漫在其周围组织中氧气和养分无法满足其进一步生长。此时，肿瘤细胞会分泌多种细胞生长因子，促发在其周围形成紊乱无序的、不成熟的新生血管，为其提供“养料”，即导致肿瘤血管新生。
刘明耀教授课题组研究发现，11－羰基－β－乙酰乳香酸通过干扰内皮细胞生长因子受体和雷帕霉素靶蛋白信号通路，抑制血管内皮细胞的增殖、迁移以及小管状结构形成，从而阻断新生血管形成，降低肿瘤的营养供应，抑制前列腺癌的生长。
据了解，乳香酸是传统中药乳香的有效活性成分，提取于卡氏乳香树的橡胶脂中，而11－羰基－β－乙酰乳香酸是乳香酸的结构衍生物。卡氏乳香树广泛分布于热带区域，在中国的海南省、台湾南部、广东南部、广西南部及云南南部等地区都有种植。
一直以来，乳香酸就被视为一种抗炎药，用于治疗关节炎、呼吸道感染等疾病，该项科学研究揭示了乳香酸能有效控制肿瘤生长这一崭新的功能和机理，提示了11－羰基－β－乙酰乳香酸这一类化合物有可能成为安全的、有效的抗肿瘤药物。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
