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 (E₂), vascular endothelial growth factor (VEGF), and 4OH-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 E₂; group 3, treated with VEGF; group 4, treated with both E₂ and VEGF; group 5, treated with E₂, 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 × 10⁵ 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.