Sheu J R, Fu C C, Tsai M L, Chung W J
Cancer Research Center, Gwo-Chyang GMP Pharmaceutical Co., Ltd., Tainan, Taiwan.
Anticancer Res. 1998 Nov-Dec;18(6A):4435-41.
A potent angiogenesis inhibitor, U-995, has been purified from the cartilage of the blue shark (Prionace glauca). U-995 is composed of two single peptides with molecular mass of 10 and 14 kDa, respectively.
U-995 was designed to study human umbilical vein endothelial cell (HUVEC) migration and proliferation in vitro and angiogenesis induced by TNF alpha in chicken chorioallantoic membrane (CAM). Furthermore, we determined the ability of U-995 to inhibiting tumor cell growth and metastasis.
U-995 (15 and 30 micrograms/ml) markedly inhibited HUVEC migration and, at 15-50 micrograms/ml produced a dose-dependent decline in [3H]-thymidine incorporation. 30 and 50 micrograms/ml of U-995, when added to TNF alpha-induced angiogenesis caused discontinuous and disrupted blood vessels. Moreover, U-995 (30 micrograms/ml) markedly prevented collagenase-induced collagenolysis. In addition, when 200 micrograms U-995 was injected i.p. into mice it suppressed sarcoma-180 cell growth and B16-F10 mouse melanoma cell metastasis in vivo.
These results suggest that the anti-angiogenic effects of U-995 may be be due to interference with the proliferation and migration of HUVECs as well as inhibition of collagenolysis, thereby leading to inhibition of both angiogenesis and tumor cell growth.
一种强效血管生成抑制剂U - 995已从蓝鲨（Prionace glauca）的软骨中纯化出来。U - 995由两种单肽组成，分子量分别为10 kDa和14 kDa。
设计U - 995用于研究人脐静脉内皮细胞（HUVEC）的体外迁移和增殖以及肿瘤坏死因子α（TNFα）在鸡胚绒毛尿囊膜（CAM）中诱导的血管生成。此外，我们测定了U - 995抑制肿瘤细胞生长和转移的能力。
U - 995（15和30微克/毫升）显著抑制HUVEC迁移，并且在15 - 50微克/毫升时使[³H] - 胸腺嘧啶核苷掺入呈剂量依赖性下降。当向TNFα诱导的血管生成中添加30和50微克/毫升的U - 995时，会导致血管不连续和破裂。此外，U - 995（30微克/毫升）显著抑制胶原酶诱导的胶原溶解。另外，当将200微克U - 995腹腔注射到小鼠体内时，它会抑制肉瘤180细胞生长和B16 - F10小鼠黑色素瘤细胞的体内转移。
这些结果表明，U - 995的抗血管生成作用可能是由于干扰HUVEC的增殖和迁移以及抑制胶原溶解，从而导致血管生成和肿瘤细胞生长均受到抑制。
