Concentration‑dependent effects of rapamycin on proliferation, migration and apoptosis of endothelial cells in human venous malformation

Si,Yameng; Chu,Hanchen; Zhu,Weiwen; Xiao,Tao; Shen,Xiang; Fu,Yu; Xu,Rongyao; Jiang,Hongbing

doi:10.3892/etm.2018.6782

Concentration‑dependent effects of rapamycin on proliferation, migration and apoptosis of endothelial cells in human venous malformation

Authors:
- Yameng Si
- Hanchen Chu
- Weiwen Zhu
- Tao Xiao
- Xiang Shen
- Yu Fu
- Rongyao Xu
- Hongbing Jiang
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Affiliations: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, College of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China
Published online on: September 19, 2018 https://doi.org/10.3892/etm.2018.6782
Pages: 4595-4601
Copyright: © Si et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rapamycin has been reported to be immunosuppressive and anti-proliferative towards vascular endothelial and smooth muscle cells. The purpose of the present study was to investigate the effects of rapamycin on the biological behaviors of endothelial cells that have been separated from the deformed vein in human venous malformation (VM). Cellular morphology was observed using inverted microscopy. An MTT assay was performed to measure the cell viability at different concentrations of rapamycin and different time points. Cell apoptosis and migration were detected using a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay and a wound‑healing assay, respectively. At 48 and 72 h, rapamycin inhibited proliferation of human VM endothelial cells, with the effects becoming more pronounced with increasing concentration. Only rapamycin at a concentration of 1,000 ng/ml had a significant effect at 24 h in repressing proliferation. At 48 h, compared with the blank group, the majority of cells maintained a clear nuclear boundary and a regular shape following treatment with 1 ng/ml rapamycin; 10 and 100 ng/ml rapamycin caused desquamation and rounded shape; and 1,000 ng/ml rapamycin caused even more marked desquamation, rounded shape and necrosis. Rapamycin at concentrations of 1, 10, 100 and 1,000 ng/ml reduced cell viability, increased the number of apoptotic cells and suppressed the migration capacity of human VM endothelial cells, and the effects became more pronounced with increasing concentration, when compared with the blank group. These findings provide evidence that rapamycin induces apoptosis and inhibits proliferation and migration of human VM endothelial cells in a concentration‑dependent manner.

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