The Inhibiting Effects Of Triptolide (PG-490) On Angiogenesis And Its Possible Mechanism

Purpose To investigate the effects of triptolide (PG-490, TP), a component of Chinese herb Tripterygium wilfordii Hook F., on the angiogenesis and its mechanism. Methods Human umbilical veinendothelial cells (HUVECs) were cultured in vitro and treated with TP (0, 5, 10, 20, 30μg/L) or dexamethasone (300 mg/L) as positive treatmentcontrol. Cells count, [~3H]—TdR incorporation, MTT assay and culture onagarose gel were used to observe the proliferation and migration of HUVECs. Three-dimensional culture system and chick embryo chorioallantoic membrane (CAM) test were applied to observe the capillary-like tube formation of HUVECs and the angiogenesis respectively. The expression of urokinase-type plasminogen activator (u-PA) and tissue-plasminogen activator (t-PA) of HUVECs were detected by immunohistochemical assay. The gene expression of u-PA was detected by real time quantitative reverse transcription polymerase chain reaction. Results TP inhibited the proliferation of HUVECs in a dose-dependent manner. TP at the concentration of 5 μg/L could inhibit 28.93% of the proliferation of HUVECs, which is more remarkable than the effect of 300 mg/L dexamethasone. TP, even at a low concentration of 5 μg/L could reduce the migration activity of HUVECs and inhibit the capillary-liketube formation of HUVECs and the angiogenesis of CAM. TP suppressed the expression of u-PA and t-PA and down-regulated gene transcription of u-PA in HUVECs. Conclusion TP inhibits ECs proliferation, migration and tube formation, the suppressing of u-PA and t-PA expression may contribute to its inhibiting effect on angiogenesis.