Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis

Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis
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β-榄香烯通过抑制血管内皮生长因子介导的血管生成来抑制黑色素瘤的生长和转移

DOI:
10.1007/s00280-010-1378-x
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发表时间:
2011-04-01
影响因子:
3
通讯作者:
Xu, Bo
Xu, Bo
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Wenxing;Lu, Yin;Xu, Bo

文献摘要

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为评价β-榄香烯在体内外的抗血管生成作用,并探讨其抑制黑色素瘤生长和转移的内在机制,采用细胞增殖实验检测β-榄香烯对B16 F10细胞的抑制作用。采用大鼠主动脉环和鸡胚绒毛尿囊膜体外血管生成试验,以及C57 BL/6小鼠黑色素瘤生长和转移试验。分别采用Western blot和酶联免疫吸附试验(ELISA)检测体外和体内血管内皮生长因子(VEGF)的表达。β-榄香烯从200 μ M开始抑制B16 BF 10细胞增殖,但VEGF从20 μ M开始抑制。20和50 μ M β-榄香烯在体外均能抑制VEGF诱导的大鼠主动脉环血管出芽和鸡胚绒毛尿囊膜微血管形成。体内实验中,腹腔注射β-榄香烯后,小鼠原发性黑色素瘤的肿瘤体积明显小于对照组;原发性黑色素瘤的CD34表达也受到抑制;肺内转移性黑色素瘤集落和黑色素含量明显减少。此外,VEGF在小鼠黑色素瘤、血清和肺组织中的表达结果也表明,VEGF在体内被抑制,β-榄香烯通过抑制VEGF介导的血管生成抑制黑色素瘤的生长和转移。它是一种天然的潜在抗血管生成剂。
It was to assess antiangiogenic effect of beta-elemene in vitro and in vivo, and it was involved in inhibiting melanoma growth and metastasis, as well as to elucidate its intrinsic mechanism.Inhibitive effect of beta-elemene on B16F10 cells was performed by cell proliferation assay. Angiogenesis assays in vitro including rat aortic ring and chick embryo chorioallantoic membrane were used, as well as melanoma growth and metastasis assay in C57BL/6 mice. Vascular endothelial growth factor (VEGF) expression in vitro and in vivo was measured respectively by western blot analysis and enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry analysis of CD34 and VEGF expression in primary melanoma was also presented.beta-Elemene inhibited B16BF10 cell proliferation starting from 200 mu M, but VEGF from 20 mu M. Both 20 and 50 mu M beta-elemene in vitro inhibited VEGF-induced sprouting vessel of rat aortic ring and microvessel formation of chick embryo chorioallantoic membrane. In vivo, tumor size of primary melanoma in mice intraperitoneally treated with beta-elemene was significantly smaller than that of the control; CD34 expression of primary melanoma was also suppressed; and the metastatic melanoma colonies and content of melanin in lung were detected obviously decreased in mice of beta-elemene-treated groups. Furthermore, results of VEGF expressing in primary melanoma, serum and lung of mice also disclosed that VEGF was inhibited in vivo.beta-Elemene inhibited melanoma growth and metastasis through suppressing VEGF-mediated angiogenesis. It is a natural potential antiangiogenic agent.