联合应用血管新生抑制剂抑制肿瘤的生长与转移
ombination of antiangiogeneses effectively inhibits cancer growth and metastasis in a xenograft model
血管新生是一个多步骤的过程,其完成依赖于内皮细胞的生长及内皮细胞与周围基质的相互作用。联合应用内皮细胞增殖抑制剂和基质抑制剂可更有效得抑制血管新生。Fumagillin是一种2型methionine aminopeptidase抑制剂而Cyclo与整合素结合可抑制内皮细胞与细胞外基质的粘附进而抑制血管新生。目的:研究Fumagillin和Cyclo联合应用对大肠癌生长、转移的抑制作用。方法:向SCID小鼠背部皮下接种大肠癌细胞,接种4周后每两日腹腔注射烟曲霉素或Cyclo 持续4周,然后处死动物并测量原发瘤重量及原发瘤内微血管密度。在体外培养脐带静脉内皮细胞(HUVECs),向培养基内加入烟曲霉素或Cyclo,观察其对HUVECs微管形成的抑制作用。结果:发现联合应用Fumagillin和Cyclo可抑制大肠癌生长和肺转移并降低肿瘤内部CD105阳性的新生血管数目。在体外脐带静脉内皮细胞亦显著得被Fumagillin和Cyclo抑制。结论:联合应用低浓度的Fumagillin和Cyclo可通过抑制血管新生而有效抑制大肠癌的生长和转移。
ngiogenesis is a cooperative process that includes endothelial growth and sprouting and interaction with the surrounding matrix. The combined use of endothelial growth inhibitor and matrix blocker expected to inhibit the angiogenesis. Antiangiogenesis is one of strategies for treating cancer. Fumagillin is an inhibitor of type 2 methionine aminopeptidase and Cyclo (Arg-Gly-Asp-D-Phe-Val), an integrin ?v?3 antagonist can block blood vessel formation. In this study, male SCID mice were injected with colon cancer cells in the subcutis and then treated with Fumagillin and Cyclo. The tumor weight, microvessel density (MVD), and number of pulmonary metastatic foci were examined. Inhibitary effect of endothelial cell growth and tube formation was examined by human umbilical endothelial cells (HUVECs), which reflect the in vivo angiogenesis. The combination of Fumagillin and Cyclo-treated mice showed the greatest effect on the tumor mass reduction, lesser number of the pulmonary metastases, and lower MVD-CD105 levels than control animals. In vitro proliferation and tube formation of HUVEC was also decreased best by the combination of both. In conclusion, The combination of Fumagillin and Cyclo at their low doses, one tenth to one hundredth was found to suppress best colorectal cancer growth and metastasis by suppressing angiogenesis.
侯力
肿瘤学基础医学药学
肿瘤学血管新生烟曲霉素
ngiogenesisFumagillinCYCLO
侯力.联合应用血管新生抑制剂抑制肿瘤的生长与转移[EB/OL].(2013-04-12)[2025-08-24].http://www.paper.edu.cn/releasepaper/content/201304-283.点此复制
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