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Piperlongumine inhibits the proliferation, migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis

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Abstract

Objectives

Recent studies have indicated that piperlongumine (PLM) may exert anti-inflammatory effects. In the present study, we determined the effect of PLM on the proliferation, apoptosis, migration and invasion of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) (referred to herein as RA FLS). We further explored the mechanisms by which the studied compound inhibits the functions of RA FLS.

Methods

RA FLS viability and apoptosis were tested using MTT and Annexin V/PI assays, respectively. We performed an EDU assay to examine the proliferation of RA FLS. The migration and invasion of these cells were measured using a transwell chamber method and wound closure assay. The MMP-1, MMP-3, and MMP-13 levels in the culture supernatants of RA FLS were detected using a Luminex Assay kit. The intracellular ROS levels were detected using DCFH-DA. The expression levels of signal transduction proteins were measured using western blot.

Results

We found that PLM induced apoptosis in RA FLS at concentrations of 15 and 20 μM. The proliferation of RA FLS was downregulated by PLM at concentrations of 1, 5 and 10 μM. Migration and invasion of RA FLS were reduced by PLM at concentrations of 1, 5 and 10 μM. PLM also inhibited cytoskeletal reorganization in migrating RA FLS and decreased TNF-α-induced intracellular ROS production. Moreover, we demonstrated the inhibitory effect of PLM on activation of the p38, JNK, NF-κB and STAT3 pathways.

Conclusions

Our findings suggest that PLM can inhibit proliferation, migration and invasion of RA FLS. Moreover, these data suggests that PLM might have therapeutic potential for the treatment of RA.

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Acknowledgements

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

Funding

This work is supported by grants from National Natural Science Foundation of China (Grant numbers 81373182, U1401222, 81501389 and 81671591), Guangdong Natural Science Foundation (Grant numbers S2011020002358, S2013010015363, and 2014A030310124) and Guangdong Project of Science and Technology (Grant numbers 2014A020212119, 2016A020215051 and 2016A020215043).

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Author notes

  1. Siqi Xu and Youjun Xiao contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, Guangdong, 510080, China

    Siqi Xu, Youjun Xiao, Shan Zeng, Yaoyao Zou, Qian Qiu, Mingcheng Huang, Zhongping Zhan, Liuqin Liang, Xiuyan Yang & Hanshi Xu

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  1. Siqi Xu
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Correspondence to Hanshi Xu.

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Responsible Editor: Jason J. McDougall.

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Xu, S., Xiao, Y., Zeng, S. et al. Piperlongumine inhibits the proliferation, migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis. Inflamm. Res. 67, 233–243 (2018). https://doi.org/10.1007/s00011-017-1112-9

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  • DOI: https://doi.org/10.1007/s00011-017-1112-9

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