Antiangiogenic potential of 10-hydroxycamptothecin.
Antiangiogenic potential of 10-hydroxycamptothecin.
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DOI：
10.1016/s0024-3205(01)01236-x
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发表时间：
2001-08
期刊：
影响因子：
6.1
通讯作者：
Dong Xiao;W. Tan;M. Li;Jian Ding
中科院分区：
文献类型：
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作者：
Dong Xiao;W. Tan;M. Li;Jian Ding
为了研究10-羟基喜树碱（HCPT）的抗血管生成潜能，采用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，并采用两种体外模型系统评估了内皮细胞的迁移和管的形成。此外，通过对鸡胚绒毛尿囊膜（CAM）实验的改进，在体内测定了对血管生成的抑制作用。荧光显微镜下观察细胞凋亡形态学变化。HCPT 0.313-5 μmol。L−1处理对HMEC细胞的增殖、迁移和管形成有剂量依赖性的抑制作用，HCPT为6.25-25 nmol。CAM实验中，卵细胞−1抑制血管生成。HCPT 1.25-5 μmol。L−1在HMEC细胞中引起典型的凋亡形态学变化，包括染色质浓缩、核断裂和体积减少。在较低浓度下，HCPT在体外和体内均能显著抑制血管生成，这种作用与诱导HMEC细胞凋亡有关。这些结果表明HCPT可能是一种有效的抗血管生成和细胞毒性药物，值得进一步研究。
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 μmol.L−1treatment resulted in a dose-dependent inhibition of proliferation, migration and tube formation in HMEC cells, and HCPT 6.25–25 nmol.egg−1inhibited angiogenesis in CAM assay. HCPT 1.25–5 μmol.L−1elicited 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.