RESUMO
Aim To investigate the effects of isoliquiri-tigenin ( ISL) on anti-angiogenesis both in vitro and in vivo and its mechanisms. Methods We assessed the antiangiogenic activities of ISL on proliferation viabili-ty, migration and tube formation of human microvascu-lar endothelial cell line-1 (HMEC-1) in vitro. The cell proliferation viability was assessed using the Sulforho-damine B ( SRB ) assay. Modified Boyden Transwell chamber assay was done to study the effect of ISL on HMEC-1 cells migration. 2′, 7′-dichlorofluorescein di-acetate ( DCFH-DA) was used to measure the levels of intracellular reactive oxygen species ( ROS ) , which was induced by VEGF. Metalloproteinase-2 ( MMP-2 ) and metalloproteinase-9 ( MMP-9 ) expressions by HMEC-1 cells were assessed through gelatin zymogra-phy assay. HMEC-1 cells cycle was detected by flow cytometry. Moreover, we investigated the in vivo anti-angiogenic activity of ISL on chicken embryos nap al-lantoic membrane model ( CAM ) . Results ISL con-centration-dependently inhibited the growth of HMEC-1 cells as well as SW620 and A549 cells. ISL signifi-cantly and concentration-dependently suppressed the migration activity of HMEC-1 cells. Tube sample struc-ture formation further confirmed the effect of ISL on an-ti-angiogenesis. Moreover, ISL also inhibited intracel-lular ROS level, MMP-2 and MMP-9 expression by HMEC-1 cells. ISL induced endothelial cell apoptosis at a low concentration ( ISL 12 . 5 μmol · L-1 ) and blocked the cells in S phase of mitosis at higher con-centrations ( ISL 25~100 μmol·L-1 ) . Furthermore, ISL distinctly inhibited the angiogenesis of chick em-bryos in vivo. Conclusions ISL has anti-tumor and angiogenesis effects on HMEC-1 cells. The mechanism may be related to intracellular ROS scavenging and ap-optosis induction of HMEC-1 cells.
RESUMO
OBJECTIVE: To assess whether there is correlation between serum concentrations of vascular endothelial growth factor(VEGF) and development of preeclampsia. METHODS: The authors measured serum concentrations of VEGF in 18 preeclamptic women admitted to Sanggye Paik Hospital, Inje University from February 1999 to September 1999 and in 18 normotensive pregnant women matched in maternal age, maternal body weight, parity and gestational age. VEGF was measured with a sensitive and specific enzyme immunoassays. RESULTS: VEGF was detected in all pregnant women. The results of this study showed that the serum concentrations of VEGF are significantly higher in the preeclamptic women than in the normotensive pregnant women. The values of median and range of VEGF are 7.74 ng/ml and 0.5-35.94 ng/ml in the preeclamptic women, and 0.5 ng/ml and 0.5-2.16 ng/ml in the normotensive pregnant women, respectively. There is significant difference in serum concentrations of VEGF between two groups(p<0.001, Mann-Whitney U test). Positive correlations were noted between VEGF concentraions and the systolic and diastolic blood pressure(Systolic BP: r2=0.688, Diastolic BP: r2=0.722, Spearman rank test). CONCLUSION: The high serum concentration of VEGF is thought to be important in the development or pathophysiologic mechanism of preeclampsia. In the next study, the prospective analysis will be necessary to identify whether serum concentration of VEGF is abnormally high in early gestational pregnant women who are destined to preeclampsia.