CYTOSTATIC INHIBITION OF ENDOTHELIAL-CELL GROWTH BY THE ANGIOGENESIS INHIBITOR TNP-470 (AGM-1470)

被引:217
作者
KUSAKA, M [1 ]
SUDO, K [1 ]
MATSUTANI, E [1 ]
KOZAI, Y [1 ]
MARUI, S [1 ]
FUJITA, T [1 ]
INGBER, D [1 ]
FOLKMAN, J [1 ]
机构
[1] HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115
关键词
D O I
10.1038/bjc.1994.41
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recently, me reported the anti-angiogenic action along with anti-tumour activity of TNP-470 (AGM-1470). In this study, the effect of TNP-470 on the growth of human umbilical vein endothelial (HUVE) cells was examined. TNP-470 inhibited the growth of HUVE cells in a biphasic manner. The inhibition was cytostatic in the first phase (complete inhibition at 300 pg ml(-1) with the IC50 of 15 pg ml(-1) and cytotoxic in the second phase (greater than or equal to 30 mu g ml(-1)). The cytostatic inhibition of HUVE cell growth by TNP-470 was durable after washing out TNP-470 in culture. Incorporation of thymidine but not uridine and leucine by HUVE cells was inhibited in the first phase, while that of all three compounds was inhibited in the second phase. Human and rat endothelial cells among various types of cells were the most sensitive to the cytostatic inhibition, while differences in the cytotoxic inhibition were minimal. These results suggest that TNP-470 exerts its specific anti-angiogenic action by inhibiting cytostatically growth of endothelial cells in a relatively specific manner.
引用
收藏
页码:212 / 216
页数:5
相关论文
共 11 条
[1]   NOVEL GROWTH REGULATORY FACTORS AND TUMOR ANGIOGENESIS [J].
BICKNELL, R ;
HARRIS, AL .
EUROPEAN JOURNAL OF CANCER, 1991, 27 (06) :781-785
[2]   TUMOR ANGIOGENESIS [J].
FOLKMAN, J .
ADVANCES IN CANCER RESEARCH, 1985, 43 :175-203
[3]   WHAT IS THE EVIDENCE THAT TUMORS ARE ANGIOGENESIS DEPENDENT [J].
FOLKMAN, J .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1990, 82 (01) :4-6
[4]   SYNTHETIC ANALOGS OF FUMAGILLIN THAT INHIBIT ANGIOGENESIS AND SUPPRESS TUMOR-GROWTH [J].
INGBER, D ;
FUJITA, T ;
KISHIMOTO, S ;
SUDO, K ;
KANAMARU, T ;
BREM, H ;
FOLKMAN, J .
NATURE, 1990, 348 (6301) :555-557
[5]  
KLAGSBRUN M, 1991, ANNU REV PHYSIOL, V53, P217, DOI 10.1146/annurev.physiol.53.1.217
[6]   POTENT ANTI-ANGIOGENIC ACTION OF AGM-1470 - COMPARISON TO THE FUMAGILLIN PARENT [J].
KUSAKA, M ;
SUDO, K ;
FUJITA, T ;
MARUI, S ;
ITOH, F ;
INGBER, D ;
FOLKMAN, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 174 (03) :1070-1076
[7]   DEVELOPMENT OF ANGIOGENESIS INHIBITORS FOR CLINICAL-APPLICATIONS [J].
MAIONE, TE ;
SHARPE, RJ .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1990, 11 (11) :457-461
[8]  
MARUI S, 1992, CHEM PHARM BULL, V40, P96
[10]   ANGIOGENESIS INHIBITION SUPPRESSES COLLAGEN ARTHRITIS [J].
PEACOCK, DJ ;
BANQUERIGO, ML ;
BRAHN, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 175 (04) :1135-1138