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Niclosamide inhibits the inflammatory and angiogenic activation of human umbilical vein endothelial cells

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Abstract

Objective

Niclosamide is known to have anti-cancer and anti-inflammatory activities; however, its therapeutic mechanism has not been defined. In this study, to explain the therapeutic mechanism of niclosamide, we examined the effect of niclosamide on endothelial cell activation, leukocyte integration, proliferation, migration and angiogenesis in vitro.

Methods

Endothelia-leukocyte adhesion assays were used to assess primary cultures of human umbilical vein endothelial cells’ (HUVECs) activation following TNF-α treatment. Each step of angiogenesis was evaluated in vitro, including endothelial cell proliferation, migration and tube formation. Proliferation was examined using EdU assays, while wound migration assays and transwell assays were used to evaluate cell migration; cord like structure formation assays on Matrigel were used to assess tube formation. In vivo matrigel plug assay was used to assess angiogenesis. The protein expression was measured using western blot.

Results

Niclosamide reduced the adhesion of human monocyte cells to HUVECs. Niclosamide also reduced protein expression of VCAM-1 and ICAM1 in HUVECs. Niclosamide significantly inhibited HUVEC proliferation, migration and cord-like structure formation. Niclosamide also suppresses VEGF-induced angiogenesis in vivo. Niclosamide attenuated IKK-mediated activation of NF-κB pathway in TNFα-induced endothelial cells. Niclosamide also suppresses VEGF-induced endothelial VEGFR2 activation and downstream P-AKT, P-mTOR and P-p70S6K.

Conclusions

Niclosamide exerted a potent effect on HUVECs activation, suggesting that it might function via an endothelia-based mechanism in the treatment of various diseases, including rheumatoid arthritis and cancer.

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Acknowledgments

The authors would like to thank Jinjin Fan for her technical assistance.

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Author notes

    Authors and Affiliations

    1. Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

      Mingcheng Huang, Qian Qiu, Shan Zeng, Youjun Xiao, Maohua Shi, Yaoyao Zou, Yujin Ye, Liuqin Liang, Xiuyan Yang & Hanshi Xu

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    1. Mingcheng Huang
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    Correspondence to Liuqin Liang.

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    No conflict of interest has been declared by authors.

    Funding

    This work is supported by grants from National Natural Science Foundation of China (Grant Number 81373182 and U1401222), Guangdong Natural Science Foundation (Grant Number S2011020002358, S2013010015363) and Guangdong Project of Science and Technology (Grant Number 2014A020212119).

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    Responsible Editor: Bernhard Gibbs.

    M. Huang and Q. Qiu contributed equally to this work.

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    Huang, M., Qiu, Q., Zeng, S. et al. Niclosamide inhibits the inflammatory and angiogenic activation of human umbilical vein endothelial cells. Inflamm. Res. 64, 1023–1032 (2015). https://doi.org/10.1007/s00011-015-0888-8

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    • DOI: https://doi.org/10.1007/s00011-015-0888-8

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