Sanguinarine inhibits VEGF-induced angiogenesis in a fibrin gel matrix
Sanguinarine inhibits VEGF-induced angiogenesis in a fibrin gel matrix
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DOI：
10.1002/biof.5520290102
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发表时间：
2007-01-01
期刊：
影响因子：
6
通讯作者：
Grasselli, Francesca
中科院分区：
文献类型：
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作者：
Basini, Giuseppina;Bussolati, Simona;Grasselli, Francesca
背景资料：目的：研究血根碱（Sanguinarine，SA）对肿瘤血管生成的抑制作用，并探讨SA对肿瘤血管生成的抑制作用。并检测了其对猪主动脉内皮细胞（AOC）Akt磷酸化的影响。在存在或不存在VEGF的情况下测试SA（300 nM（100纳克/毫升）在三维血管生成生物测定中，在加入以下物质之前，将AOC在纤维蛋白原溶液中的微载体珠上的悬浮液移液凝血酶在48、96、144、192 h测定内皮细胞增殖。结果：在所有检测时间，SA的加入消除了（p < 0.001）VEGF对AOC生长的刺激作用。结论：SA可能是一种直接抑制VEGF对内皮细胞增殖作用的天然产物，其作用可能是通过阻断VEGF诱导的Akt活化而实现的。
Background: The identification of possible ways to block blood vessels formation has become a major scientific objective of the last decade and several phytochemicals are currently being exploited to target tumour angiogenesis.Aim: The effects of Sanguinarine (SA), an alkaloid from the root of Sanguinaria Canadensis, were evaluated in an in vitro angiogenesis model; moreover the effects on Akt phosphorylation in porcine aortic endothelial cell line (AOC) were also examined.Methods: SA (300 nM) was tested in the presence or absence of VEGF (100 ng/ml) in a three dimensional angiogenesis bioassay obtained pipetting a suspension of AOC on microcarrier beads in a fibrinogen solution before the addition of thrombine. Endothelial cell proliferation was measured at 48, 96, 144, 192 h. The phosphorylation of Akt was measured by ELISA in 2 x 105 AOC treated as described above.Results: The addition of SA abolished (p < 0.001) VEGF stimulatory effect on AOC growth at all the examined times. In addition, the stimutlatory effect induced by VEGF on Akt phosphorylation was significantly (p < 0.001) inhibited by SA.Conclusion: SA appear to be an antiangiogenic natural product by directly suppressing the proliferative effect of VEGF on endothelial cell line: this effect could be mediated by blocking the VEGF-induced Akt activation.