Hu G F
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9791-5. doi: 10.1073/pnas.95.17.9791.
A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy.
通过对血管生成素（一种强效血管生成因子）作用机制的研究，已发现一类血管生成抑制剂。新霉素是一种氨基糖苷类抗生素，可抑制人血管生成素在人内皮细胞中的核转位，这是血管生成素诱导血管生成的关键步骤。新霉素的磷脂酶C抑制活性似乎与之有关，因为另一种磷脂酶C抑制剂U - 73122也有类似作用。相比之下，酪氨酸激酶抑制剂染料木黄酮、磷酸酪氨酸磷酸酶抑制剂氧代苯胂和蛋白激酶C抑制剂星形孢菌素均不抑制血管生成素的核转位。新霉素以剂量依赖方式抑制血管生成素诱导的人内皮细胞增殖。在50微摩尔时，新霉素可消除血管生成素诱导的增殖，但不影响基础增殖水平和细胞活力。其他氨基糖苷类抗生素，包括庆大霉素、链霉素、卡那霉素、阿米卡星和巴龙霉素，对血管生成素诱导的细胞增殖均无影响。最重要的是，新霉素在每枚鸡蛋低至20纳克的剂量下就能完全抑制血管生成素在鸡胚绒毛尿囊膜上诱导的血管生成。这些结果表明，新霉素及其类似物是一类有望开发用于抗血管生成素治疗的药物。
