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机构地区:[1]中国医学科学院,中国协和医科大学医药生物技术研究所,北京100050
出 处:《药学学报》2004年第4期254-258,共5页Acta Pharmaceutica Sinica
基 金:ChinaStateKeyBasicResearch 973Project(G1 998051212);NationalFoundationforCancerResearchofUSA
摘 要:目的 研究大黄素对血管生成的抑制作用及相关作用机制。方法 用鸡胚观察药物对血管生成的影响 ;用培养的内皮细胞检测大黄素抑制细胞增殖和诱导细胞凋亡作用。结果 大黄素 150和 3 0 0 μg egg对鸡胚的血管生成的抑制率分别为 3 7 6%和 63 2 %。大黄素抑制内皮细胞增殖 ,在有bFGF、无bFGF、有VEGF的条件下 ,其IC5 0 值分别为 5 56,8 40和 6 91mg·L- 1。大黄素可诱导内皮细胞凋亡 ,并可干扰内皮细胞周期 ,出现G2 M期阻滞 ;可导致CyclinB1,P3 4 cdc2 和Bcl 2等蛋白的表达下调 ,但对Bax的表达无影响。结论 大黄素有抑制血管生成作用 。AimTo determine the anti-angiogenic activity of emodin. MethodsChick embryo assay and cultured endothelial cells were used. ResultsEmodin at doses of 150 and 300 μg/egg caused 37 6% and 63 2% inhibition of an giogenesis, respectively. Emodin was shown to inhibit the proliferation of prima ry cultured bovine aortic endothelial cells in the absence or presence of basic -fibroblast growth factor (bFGF) or the presence of vascular endothelial growth factor (VEGF) in a dose-dependent manner. The IC 50 values by MTT assay w ere 5 56 , 8 40 or 6 91 mg·L -1 , respectively. Emodin at concentra tions from 5 4 to 21 6 mg·L -1 induced apoptosis of endothelial cel ls for 37 6% to 72 6%. Emodin caused endothelial cell cycle arrest at G 2/M phase. After emodin treatment, there was a down-regulation of Cyclin B1, P34 cdc2 , and Bcl-2 protein expression while the Bax protein expression was u naffected. ConclusionEmodin shows anti-angiogenic activity and might be useful for the development o f novel anti-cancer therapy.
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