ACTIBIND, a T2 RNase, competes with angiogenin and inhibits human melanoma growth, angiogenesis, and metastasis
ACTIBIND, a T2 RNase, competes with angiogenin and inhibits human melanoma growth, angiogenesis, and metastasis
复制标题
DOI：
10.1158/0008-5472.can-07-0129
复制
发表时间：
2007-06-01
期刊：
影响因子：
11.2
通讯作者：
Bar-Eli, Menashe
中科院分区：
文献类型：
--
作者：
Schwartz, Betty;Shoseyov, Oded;Bar-Eli, Menashe
黑色素瘤是一种非常具有侵袭性和高度血管生成的肿瘤，其中标准治疗仅取得有限的成功。晚期患者的5年生存率为5%。为了寻找替代品，我们确定了一种从真菌黑曲霉中提取的天然产物，称为ACTIBIND，可抑制体内黑色素瘤的肿瘤生长和转移。ACTIBIND是一种T-2 RNA酶，通过与血管生成因子血管生成素（本身是RNA酶同源物）竞争发挥抗肿瘤和抗血管生成活性。因此，在黑色素瘤和血管内皮细胞中基质金属蛋白酶2的表达和活性降低，血管形成减少，体内肿瘤细胞凋亡增加。在使用含有血管生成素的海绵进行的体内血管生成试验中，爱替宾显著抑制血管生成。在体外，ACTIBIND被黑色素瘤和人脐静脉内皮细胞内化，到达细胞核，并以剂量依赖性方式抑制血管生成素反应元件的活性。总的来说，我们的数据表明，爱替宾作为一种新的抗血管生成治疗黑色素瘤的方式，其潜力应进行测试。
Melanoma is a very aggressive and highly angiogenic tumor in which standard treatments have had only limited success. Patients with advanced disease have a 5-year survival rate of 5%. In search for alternatives, we identified a natural product extracted from the fungus Aspergillus niger, termed ACTIBIND, that inhibits tumor growth and metastasis of melanoma in vivo. ACTIBIND, a T-2 RNase, exerts antitumorigenic and antiangiogenic activities by competing with the angiogenic factor angiogenin (itself an RNase homologue). Thus, there was decreased expression and activity of the matrix metalloproteinase 2 in melanoma and vascular endothelial cells, decreased vascularization, and increased tumor cell apoptosis in vivo. ACTIBIND significantly inhibited angiogenesis in an in vivo angiogenesis assay with sponges containing angiogenin. In vitro, ACTIBIND was internalized by both melanoma and human umbilical vein endothelial cells, reached the cell nuclei, and inhibited the activity of angiogenin response elements in a dose-dependent manner. Collectively, our data indicate that ACTIBIND should be tested for its potential as a new antiangiogenic modality for the treatment of melanoma.