# Recombinant Human Endostatin Suppressed the Biological Behavior of Human Umbilical Vein Endothelial Cells Under Hypoxic and Hypoxic/Starvation Conditions In Vitro

## TL;DR

This study shows that recombinant human endostatin suppresses the growth and activity of human umbilical vein endothelial cells under low oxygen and starvation conditions in the lab.

## Contribution

The study reveals rh-endostatin's effect on normal endothelial cells under hypoxic and starvation conditions, which is rarely reported.

## Key findings

- Rh-endostatin inhibited HUVEC proliferation, migration, and tube formation under normoxic, hypoxic, and H/S conditions.
- CD105 expression was upregulated in starvation and H/S groups but downregulated by rh-endostatin across all conditions.
- Rh-endostatin did not enhance its effect with higher concentrations and did not promote malignant behavior.

## Abstract

Recombinant human endostatin (rh-endostatin) has been shown to act as an inhibitor of angiogenesis. Previous studies have indicated that rh-endostatin combined with chemotherapy can improve the objective response rate (ORR), time to progression (TTP), and clinical benefit rate (CBR) without increasing toxicity. However, this function has seldom been reported in normal cells. The aim of our study was to explore the effect of rh-endostatin on the biological behavior of human umbilical vein endothelial cells (HUVECs) under different conditions in vitro. Confluent HUVECs were cultured under normoxic, hypoxic, or hypoxic/starvation (H/S) conditions and then treated with rh-endostatin. An MTT assay was used to assess cell proliferation, and HUVEC tube formation and migration were assessed via a cell tubule formation assay and a migration assay. The expression of endoglin (CD105) was assessed by flow cytometry (FCM). Rh-endostatin inhibited the proliferation, migration, and tube formation of HUVECs under normoxic, hypoxic, and H/S conditions. Compared with that in the normoxia group, the expression of CD105 was not different in the hypoxia 24 h group, but in the starvation and hypoxia/starvation groups, the expression of CD105 was upregulated. Rh-endostatin downregulated the expression of CD105 under all the study conditions. Here we found rh-endostatin suppressed the biological behavior of HUVECs under hypoxic and H/S conditions. As the concentration increased, the effect of rh-endostatin on the biological behavior of HUVECs was not greatly enhanced. Rh-endostatin did not promote malignant biological behavior or CD105 expression. Since CD105 may induce endothelial-to-mesenchymal transition in HUVECs, we hypothesized that rh-endostatin may inhibit the malignant biological behavior of HUVECs under hypoxic conditions in vitro.