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Antiangiogenic potential of 10-hydroxycamptothecin.

机译:10-羟基喜树碱的抗血管生成潜力。

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To investigate the antiangiogenic potential of 10-hydroxycamptothecin (HCPT), the proliferation of human microvascular endothelial cells (HMEC) and seven human tumor cell lines were detected by SRB assay, and the endothelial cell migration and tube formation were assessed using two in vitro model systems. Also, inhibition of angiogenesis was determined with a modification of the chick embryo chorioallantoic membrane (CAM) assay in vivo. Morphological assessment of apoptosis was performed by fluorescence microscope. HCPT 0.313-5 micromol x L(-1) treatment resulted in a dose-dependent inhibition of proliferation, migration and tube formation in HMEC cells, and HCPT 6.25-25 nmol x egg(-1) inhibited angiogenesis in CAM assay. HCPT 1.25-5 micromol x L(-1) elicited typical morphological changes of apoptosis including condensed chromatin, nuclear fragmentation, and reduction in volume in HMEC cells. HCPT significantly inhibited angiogenesis both in vitro and in vivo at relatively low concentrations, and this effect was related with induction of apoptosis in HMEC cells. These results taken collectively suggest that HCPT may be a potent antiangiogenetic and cytotoxic drug and further investigation is warranted.
机译:为了研究10-羟基喜树碱(HCPT)的抗血管生成潜力,通过SRB法检测了人微血管内皮细胞(HMEC)和7种人肿瘤细胞系的增殖,并使用两种体外模型评估了内皮细胞迁移和管形成系统。同样,通过修饰体内鸡胚绒膜尿囊膜(CAM)测定法来确定对血管新生的抑制作用。通过荧光显微镜进行凋亡的形态学评估。 HCPT 0.313-5 micromol x L(-1)处理导致HMEC细胞增殖,迁移和管形成呈剂量依赖性抑制,而HCPT 6.25-25 nmol x egg(-1)在CAM分析中抑制血管生成。 HCPT 1.25-5 micromol x L(-1)引起凋亡的典型形态变化,包括染色质浓缩,核碎裂和HMEC细胞体积减少。 HCPT在相对较低的浓度下在体内和体外均显着抑制血管生成,并且这种作用与诱导HMEC细胞凋亡有关。这些共同得​​出的结果表明,HCPT可能是一种有效的抗血管生成和细胞毒性药物,有待进一步研究。

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