[Effect of triptolide on expression of urokinase-type plasminogen activators in vascular endothelial cells].
OBJECTIVE
It has been showed that triptolide (T10) has antitumor activities. This study was to observe the inhibitory effects of T10 on proliferation of vascular endothelial cells and expression of urokinase-type plasminogen activator (u-PA), and to elucidate the antiangiogenic mechanism of T10.


METHODS
Human umbilical vein endothelial cells were cultured in vitro for 3 generations, and treated with T10 (0, 5, 10, 20, and 30 microg/L), or dexamethasone (300 mg/L) as control. Cell count and 3H-TDR incorporation were used to observe cell proliferation. The chick embryo chorioallantoic membrane (CAM) test was carried out to observe the effect of T10 on angiogenesis. Immunohistochemistry and real-time quantitive reverse transcription-polymerase chain reaction (RT-PCR) were used to detect protein and mRNA levels of u-PA.


RESULTS
T10 inhibited the proliferation of umbilical vein endothelial cells in a dose-dependent manner; inhibitory rate of endothelial cells was 28.93% after treatment of 5 microg/L of T10. T10 significantly reduced angiogenesis in CAM, even at the concentration of 5 microg/L (P<0.05). T10 decreased protein and mRNA levels of u-PA in endothelial cells in a dose-dependent manner; the protein level of u-PA was reduced by 41.05% after treatment of 5 microg/L of T10.


CONCLUSIONS
T10 could inhibit the proliferation of human umbilical vein endothelial cells and expression of u-PA, which may contribute to its antiangiogenic activity.
Ding
Yi
Y
Department of Pathophysiology, Sichuan University, Chengdu, Sichuan, 610041, PR China.
Zhang
Jie
J
Zhao
Qing-Liang
QL
Hou
Li-Jun
LJ
Wang
Qiu-Lin
QL
Wang
Shu-Ren
SR
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004852:Epoxy Compounds; D006801:Humans; D009389:Neovascularization, Pathologic; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D029757:Tripterygium / Q000737:chemistry; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D020533:Angiogenesis Inhibitors; D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D012333:RNA, Messenger; C001899:triptolide; D014568:Urokinase-Type Plasminogen Activator