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

Research paper by Mingcheng M Huang, Qian Q Qiu, Shan S Zeng, Youjun Y Xiao, Maohua M Shi, Yaoyao Y Zou, Yujin Y Ye, Liuqin L Liang, Xiuyan X Yang, Hanshi H Xu

Indexed on: 27 Oct '15Published on: 27 Oct '15Published in: Inflammation Research



Abstract

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.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 evaluatedin 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.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.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.