Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice
Bee venom inhibits tumor angiogenesis and metastasis by inhibiting tyrosine phosphorylation of VEGFR-2 in LLC-tumor-bearing mice
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DOI：
10.1016/j.canlet.2009.11.013
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发表时间：
2010-06-01
期刊：
影响因子：
9.7
通讯作者：
Lee, Jae-Dong
中科院分区：
文献类型：
--
作者：
Huh, Jeong-Eun;Baek, Yong-Hyeon;Lee, Jae-Dong
蜂毒疗法是东方医学中蜂毒在治疗各种疾病中的应用。在目前的工作中，作者使用体外模型和体内小鼠血管生成和肺转移模型研究了BV作为血管生成抑制剂的功能特异性。BV显著抑制刘易斯肺癌（LLC）细胞的活力，但不影响外周血单核淋巴细胞（PBML）细胞。BV还抑制血管内皮生长因子（VEGF）诱导的人脐静脉内皮细胞（HUVECs）的增殖、迁移和毛细血管样管形成。Western blotting结果显示，BV可抑制LLC细胞和HUVECs中Ala和MAPK的磷酸化，下调LLC细胞和HUVECs中VEGF和VEGFR-2的表达。此外，在我们的体内血管生成试验中，BV有效地破坏了基质胶塞中VEGF诱导的新血管形成。BV皮下给药后，通过抑制LLC模型中的VEGF和VEGFR-2，也显著抑制肿瘤血管生成。用1 μ g/ml或10 μ g/ml BV处理携带皮下LLC肿瘤的小鼠。他们显示原发性肿瘤体积减少49%至62%，自发性肺转移发生率减少。此外，在原发性肿瘤切除后自发性肺转移模型中，BV治疗将其中位生存时间从27天延长至58天。这些结果表明BV通过阻断VEGFR-2的酪氨酸磷酸化而在肿瘤进展的不同阶段发挥肿瘤特异性抗血管生成活性，验证了BV在肺癌治疗中的应用。(C)2009年由Elsevier爱尔兰有限公司出版。
Bee venom (BV) treatment is the therapeutic application of honeybee venom (HBV) for treating various diseases in Oriental medicine. In the present work, the authors investigated the functional specificity of BV as an angiogenesis inhibitor using in vitro models and in vivo mouse angiogenesis and lung metastasis models. BV significantly inhibited the viability of Lewis lung carcinoma (LLC) cells but did not affect peripheral blood mononuclear lymphocytes (PBML) cells. BV also inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). Western blotting analysis showed that BV inhibited Ala and MAPK phosphorylation in LLC cells and HUVECs and down regulated expression of VEGF and VEGFR-2 of LLC cells and HUVECs. Also, BV effectively disrupted VEGF-induced neovascularization in Matrigel plugs in our in vivo angiogenesis assay. When given subcutaneously, BV also significantly suppressed tumor angiogenesis through inhibition of VEGF and VEGFR-2 in LLC model. Mice bearing subcutaneous LLC tumors were treated with 1 mu g/ml or 10 mu g/ml of BV. They showed reductions ranging between 49% and 62% in primary tumor volume and reduction of spontaneous pulmonary metastasis occurrences. Furthermore, BV treatment in the spontaneous lung metastases model after primary tumor excision prolonged their median survival time from 27 to 58 days. These results suggest that the tumor-specific anti-angiogenic activity of BV takes effect during different stages of tumor progression by blocking the tyrosine phosphorylation of VEGFR-2, and validate the application of BV in lung cancer treatment. (C) 2009 Published by Elsevier Ireland Ltd.