ANTISENSE INHIBITION OF UROKINASE REDUCES SPREAD OF HUMAN OVARIAN-CANCER IN MICE

被引:87
作者
WILHELM, O [1 ]
SCHMITT, M [1 ]
HOHL, S [1 ]
SENEKOWITSCH, R [1 ]
GRAEFF, H [1 ]
机构
[1] TECH UNIV MUNICH,KLINIKUM RECHTS ISAR,INST NUKL MED,MUNICH,GERMANY
关键词
INVASION; LIPOSOMES; OLIGONUCLEOTIDES; PROTEASES; THERAPY;
D O I
10.1007/BF00133485
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Urokinase-type plasminogen activator (uPA) is a protease involved in the process of tissue remodelling and cell migration in vitro. To explore whether uPA is a prerequisite for human ovarian cancer spread in vivo the expression of uPA was suppressed in human ovarian cancer cells by antisense phosphorothioate oligonucleotides (PS-ODN). The suppression of uPA expression was dependent on PS-ODN concentration and only observed in the presence of liposomes. This phenomenon seemed to be due to the fact that PS-ODNs were taken up by the cancer cells only in concert with liposomes as studied by fluorescently-labeled PS-ODNs using flow cytofluorometry and laser scanning microscopy. uPA-deprived cancer cells exhibited a significantly reduced invasive capacity in vitro compared with untreated cancer cells or cells treated with control PS-ODNs (P=0.003). The intraperitoneal spread of the cancer cells in vivo was significantly diminished when nude mice were treated with uPA antisense PS-ODNs in comparison with control mice (P=0.009). These results suggest that uPA expression may be required for spread of human ovarian cancer and that its inhibition could provide a therapeutic approach.
引用
收藏
页码:296 / 302
页数:7
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