Synergistic effect of estrogen and VEGF on the proliferation of hemangioma vascular endothelial cells

Purpose: The aim of this study was to observe the influences of estradiol (E-2), vascular endothelial growth factor (VEGF), and 40H-tamoxifen (TAM) on the proliferation of hemangioma vascular endothelial cells (HVECs). Methods: Two strawberry hemangiomas with positive estrogen receptor staining from 2 infants (cases 1 & 2) were used for HVECs culture. The HVECs of passage 3 were cultured in estrogen-free improved minimum essential medium and divided into 5 groups based on different treatments: group 1, no treatment; group 2, treated with E-2; group 3, treated with VEGF; group 4, treated with both E-2 and VEGF; group 5, treated with E-2, VEGF, and TAM. Cell count (CC) and DNA proliferation index (PI) were determined on culture days 0, 3, 6, and 9. Results: On day 9 in case 1, CC and PI were the following: in group 1, 1.15 +/- 0.18 x 10(5) mL and 19.96% +/- 1.45%, respectively, presenting no statistically significant changes; in group 2, 1.38 and 1.61 times those of group 1, respectively (P < .01); in group 3, 2.10 and 1.61 times those of group 2, respectively (P < .01); in group 4, 1.62 and 1.40 times as high as with group 3, respectively (P < .01); in group 5, down to the levels of group 1. The results in case 2 were similar to those in case 1. Conclusions: In vitro,the promoting effect of VEGF on HVECs proliferation is stronger than that of estrogen. Estrogen and VEGF enhance this proliferation in a synergistic fashion, which can be inhibited by tamoxifen. (C) 2004 Elsevier Inc. All rights reserved.