Research Papers:

Effect of captopril on radiation-induced TGF-β1 secretion in EA.Hy926 human umbilical vein endothelial cells

Jingni Wei, Hui Xu, Yinyin Liu, Baiyu Li and Fuxiang Zhou _

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Oncotarget. 2017; 8:20842-20850. https://doi.org/10.18632/oncotarget.15356

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Jingni Wei1,2,4,*, Hui Xu1,2,3,*, Yinyin Liu2, Baiyu Li2, Fuxiang Zhou1,2,3

1Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

2Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

3Hubei Clinical Cancer Study Centre, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

4Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China

*These authors contributed equally to this work

Correspondence to:

Fuxiang Zhou, email: [email protected]

Keywords: irradiation, EA.Hy926, TGF-β1, captopril, NF-κB

Received: April 23, 2016     Accepted: January 27, 2017     Published: February 15, 2017


The pathophysiological mechanism involved in the sustained endothelial secretion of cytokines that leads to fibrosis 6–16 months after radiotherapy remains unclear. Angiotensin II (Ang II) is produced by the endothelium in response to stressing stimuli, like radiation, and may induce the synthesis of TGF-β, a profibrotic cytokine. In this study we tested the hypothesis that captopril, an angiotensin-converting enzyme (ACE) inhibitor, inhibits or attenuates radiation-induced endothelial TGF-β1 secretion. The human endothelial hybrid cell line EA.HY926 was irradiated with split doses of x-rays (28 Gy delivered in 14 fractions of 2 Gy). TGF-β1 mRNA, TNF-α mRNA and TGF-β1 protein levels were evaluated by RT-PCR and western blotting each month until the fifth month post radiation. Ang II was detected using radioimmunoassays, NF-κB activity was examined using EMSA, and western blotting was used to detect the expression of Iκ-Bα. To explore the role of Ang II on radiation-induced TGF-β1 release and Iκ-Bα expression, captopril was added to cultured cells before, during, or after irradiation. Sustained strong expression of TGF-β1 was observed after conventional fractionated irradiation. TNF-α, Ang II, and NF-κB activity were also increased in EA.Hy926 cells after radiation. Captopril decreased Ang II expression, inhibited the NF-κB pathway and reduced TGF-β1 expression. These data suggest that captopril might protect the endothelium from radiation-induced injury.

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