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新生霉素抑制血管生成及其与长春新碱的协同作用
引用本文:杨军,江敏,甄永苏.新生霉素抑制血管生成及其与长春新碱的协同作用[J].药学学报,2003,38(10):731-734.
作者姓名:杨军  江敏  甄永苏
作者单位: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
基金项目:国家重点基础性研究 973项目基金(G19980 512 12 ),美国癌症研究基金会 (NFCR)资助项目
摘    要:目的研究新生霉素的抑制血管生成作用及其机制。方法以鸡胚尿囊膜模型测定对血管生成的作用,并分别用MTT法、明胶酶谱法等观察新生霉素对于内皮细胞和肺癌PG细胞的影响。结果新生霉素200 μg/egg对鸡胚尿囊膜血管生成的抑制率为68.7%,且呈浓度依赖性抑制内皮细胞的增殖、运动、MMP-2分泌以及管腔的形成;新生霉素和长春新碱对血管生成及PG细胞的增殖均有明显的协同作用。结论本研究首次确定新生霉素具有抑制血管生成活性,与长春新碱联合可增强对血管生成的抑制作用。

关 键 词:新生霉素  血管生成  基质金属蛋白酶  长春新碱
收稿时间:2002-11-06

Novobiocin inhibits angiogenesis and shows synergistic effect with vincristine
YANG Jun,JIANG Min,ZHEN Yong-su.Novobiocin inhibits angiogenesis and shows synergistic effect with vincristine[J].Acta Pharmaceutica Sinica,2003,38(10):731-734.
Authors:YANG Jun  JIANG Min  ZHEN Yong-su
Affiliation:Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Abstract:AIM: To study the anti-angiogenic activity of novobiocin and its mechanism of action. METHODS: The anti-angiogenic activity of novobiocin was determined using chick embryo chorioallantoic membrane(CAM) assay. MTT assay, zymography and related assays were used to observe the effects of drugs on bovine aorta endothelial cells and human pulmonary carcinoma PG cells. RESULTS: Novobiocin at the doses of 100 and 200 micrograms/egg inhibited angiogenesis by 31.6% and 68.7% in CAM, respectively. The combination of novobiocin and vincristine enhanced the anti-angiogenic effect. Novobiocin inhibited the proliferation of bovine aortic endothelial cells in a concentration-dependent manner. In addition, novobiocin suppressed MMP-2 secretion, migration, and tube formation of endothelial cells. As determined by MTT assay, novobiocin in combination with vincristine displayed synergistic effect on the proliferation of PG cells, CONCLUSION: This study demonstrates that novobiocin is active in suppressing angiogenesis and the anti-angiogenic activity may be enhanced by combination with vincristine. The anti-angiogenic activity of novobiocin may be related, at least in part, to its inhibition of cell proliferation, cell migration, tube formation and secretion of matrix metalloproteinases.
Keywords:novobiocin  angiogenesis  matrix metalloproteinase  vincristine
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