腐胺
亚精胺
鸟氨酸脱羧酶
血管生成
生物
绒毛尿囊膜
多胺
细胞生长
DNA合成
内皮干细胞
分子生物学
细胞内
生物化学
细胞生物学
体外
癌症研究
酶
作者
Mutsumi Takigawa,M Enomoto,Y Nishida,H O Pan,A Kinoshita,F Suzuki
出处
期刊:PubMed
日期:1990-07-01
卷期号:50 (13): 4131-8
被引量:21
摘要
alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, inhibited B16 melanoma-induced angiogenesis in chick embryo chorioallantoic membrane and subsequently the growth of the tumor on the chorioallantoic membrane. These inhibitions were reversed by exogenous putrescine and spermidine. DFMO also inhibited rapid neovascularization in yolk sac membrane of 4-day-old chick embryos and the inhibition was reversed by exogenous putrescine and spermidine. DFMO strongly inhibited DNA synthesis and proliferation of bovine pulmonary artery endothelial (BPAE) cells in culture and decreased their ornithine decarboxylase activity and intracellular polyamine concentrations. Addition of putrescine to the culture medium of DFMO-treated BPAE cells restored their intracellular putrescine and spermidine concentrations and their DNA synthesis and proliferation. Addition of spermidine to cultures of DFMO-treated BPAE cells restored their intracellular spermidine concentration and their DNA synthesis and proliferation. DFMO inhibited the proliferation of B16 melanoma cells in culture but the inhibitory effect was much less than that on BPAE cells. When one-half the monolayer of confluent cultures of BPAE cells had been peeled off, addition of DFMO to the cultures inhibited the proliferation and extension of the BPAE cells into the vacant area but had no effect on stationary cells in the remaining half of the monolayer, suggesting that it inhibited induction of proliferation of endothelial cells. These findings suggest that the antitumor activity of DFMO against solid tumors is probably due more to its inhibition of tumor-induced angiogenesis by inhibition of proliferation of endothelial cells induced by polyamine depletion than to a direct effect on tumor cell proliferation.
科研通智能强力驱动
Strongly Powered by AbleSci AI