Danshensu has anti-tumor activity in B16F10 melanoma by inhibiting angiogenesis and tumor cell invasion
Danshensu has anti-tumor activity in B16F10 melanoma by inhibiting angiogenesis and tumor cell invasion
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丹参素通过抑制血管生成和肿瘤细胞侵袭对 B16F10 黑色素瘤具有抗肿瘤活性
DOI：
10.1016/j.ejphar.2010.06.045
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发表时间：
2010-09-25
影响因子：
5
通讯作者：
Wang, Ai-yun
中科院分区：
文献类型：
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作者：
Zhang, Li-juan;Chen, Lei;Wang, Ai-yun
丹参素是丹参的主要水溶性成分，是多种丹酚酸的基本化学结构。本研究通过一系列体内外模型评价丹参素的抗肿瘤活性。用四甲基偶氮唑盐比色法检测丹参素对B16F10黑色素瘤细胞和HUVEC增殖的影响，用Transwell小室实验观察丹参素对细胞侵袭和迁移的影响。通过HUVEC迁移实验、血管形成实验和鸡绒毛膜尿囊膜实验评价丹参素对血管生成的影响。用免疫印迹法检测丹参素作用后B16F10黑色素瘤细胞中基质金属蛋白酶-2、-9和血管内皮生长因子的表达。采用B16F10黑色素瘤自发转移模型和实验性黑色素瘤转移模型评价丹参素在体内转移中的作用。丹参素对B16F10黑色素瘤细胞和HUVEC的增殖无抑制作用，但对B16F10黑色素瘤细胞的侵袭(0.05、0.5、5mM)和迁移(0.5mM、5mM)有明显的抑制作用。它还显著抑制了血管内皮生长因子诱导的血管内皮细胞迁移(0.5，5微米)、体外血管形成(4，20微米)和体内血管形成(100微克/粒)。丹参素(5，50公里)显著下调B16F10黑色素瘤细胞中基质金属蛋白酶-2、-9和血管内皮生长因子的蛋白表达。在动物模型中，丹参素(20、40 mg/kg)对自发(46天)和实验性(23天)B16F10黑色素瘤转移模型的肺转移也有抑制作用。以上结果提示，丹参素可能通过影响肿瘤血管生成和肿瘤侵袭而发挥抗肿瘤作用。(C)2010爱思唯尔B.V.保留所有权利。
Danshensu, the major water-soluble component of Radix Salviae Miltiorrhizae (Danshen), is the basic chemical structure of various salvianolic acids. This study was to evaluate the anti-tumor activity of danshensu in a series of in vitro and in vivo models. The effect of danshensu on B16F10 melanoma cell and HUVEC proliferation were assessed by MTS assay, and cell invasion and migration were investigated by transwell chamber assay. The effect of danshensu on angiogenesis was evaluated by HUVEC migration assay, tube formation assay and chick chorioallantoic membrane assay. The expression of MMP-2, -9 and VEGF in B16F10 melanoma cell were detected by western blotting after danshensu treatment. The role of danshensu in tumor metastasis in vivo was evaluated by spontaneous and experimental B16F10 melanoma metastasis model. Although danshensu had no inhibitory effect on B16F10 melanoma cell and HUVEC proliferation, it significantly inhibited B16F10 melanoma cell invasion (at 0.05, 0.5, 5 mu M) and migration (at 0.5, 5 mu M). It also dramatically suppressed VEGF-induced endothelial migration (at 0.5, 5 mu M), tube formation in vitro (at 4, 20 mu M) and new vessel formation in CAM in vivo (100 mu g/egg). Danshensu (at 5, 50 KM) significantly down-regulates protein expression of MMP-2, -9 and VEGF in B16F10 melanoma cell. In animal model, danshensu (20, 40 mg/kg) also possessed inhibitory effect on lung metastasis in spontaneous (46-day treatment) and experimental (23-day treatment) B16F10 melanoma metastasis model. All these results suggest that danshensu has anti-tumor activity by affecting on tumor angiogenesis and tumor invasion. (C) 2010 Elsevier B.V. All rights reserved.