Inflammation Research

, Volume 67, Issue 3, pp 233–243 | Cite as

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

  • Siqi Xu
  • Youjun Xiao
  • Shan Zeng
  • Yaoyao Zou
  • Qian Qiu
  • Mingcheng Huang
  • Zhongping Zhan
  • Liuqin Liang
  • Xiuyan Yang
  • Hanshi Xu
Original Research Paper
  • 208 Downloads

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.

Keywords

Piperlongumine Proliferation Migration and invasion Fibroblast-like synoviocytes Rheumatoid arthritis 

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

No conflict of interest has been declared by authors.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Siqi Xu
    • 1
  • Youjun Xiao
    • 1
  • Shan Zeng
    • 1
  • Yaoyao Zou
    • 1
  • Qian Qiu
    • 1
  • Mingcheng Huang
    • 1
  • Zhongping Zhan
    • 1
  • Liuqin Liang
    • 1
  • Xiuyan Yang
    • 1
  • Hanshi Xu
    • 1
  1. 1.Department of Rheumatology, The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

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