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Chinese Journal of Integrative Medicine

, Volume 25, Issue 11, pp 837–844 | Cite as

Paeoniflorin Inhibits Migration- and Invasion-Promoting Capacities of Gastric Cancer Associated Fibroblasts

  • Zhen-fei Wang
  • Da-guang Ma
  • Ling Wang
  • Li Feng
  • Jian-wei Fu
  • Ying Li
  • Dan-ting Wang
  • Yong-feng JiaEmail author
Original Article

Abstract

Objective

To investigate the inhibitory effects of paeoniflorin on migration- and invasion-promoting capacities of gastric cancer associated fibroblasts (GCAFs) and to explore the molecular mechanism underlying the effects.

Methods

Paired gastric normal fifbroblast (GNF) and GCAF cultures were established from resected tissues. GCAFs were treated with control medium, or 2.5, 5 or 10 μg/mL paeoniflorin. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs and paeoniflorin-treated GCAFs, and used to culture AGS human gastric cancer cells. The migration and invasion capacities of AGS cells were determined with wound healing test and transwell invasion assay, respectively. The interleukin 6 (IL-6) mRNA and microRNA-149 expression in GCAFs were detected by reverse transcription-quantitative polymerase chain reaction. The IL-6 protein expression and secretion by GCAFs were measured with Western blot and enzyme-linked immunosorbent assay analysis, respectively. The protein levels of phosphorylated signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase (MMP) and MMP9 in AGS cells were examined by Western blot.

Results

GCAFs displayed enhanced capacities to induce AGS cell migration and invasion as compared with GNFs. Paeoniflorin treatment significantly inhibited the migration- and invasion-promoting capacities of GCAFs (P<0.05). GCAFs produced and secreted more IL-6 into the conditioned medium than GNFs, leading to over-activation of STAT3-MMP signaling in AGS cells. Paeoniflorin suppressed IL-6 production and secretion by up-regulating microRNA149 expression in GCAFs, and subsequently prevented GCAFs from activating IL-6-STAT3-MMP signaling of AGS cells.

Conclusions

Paeoniflorin inhibits the migration- and invasion-promoting capacities of GCAFs by targeting microRNA-149 and IL-6. Paeoniflorin is potentially a novel therapeutic agent against cancer microenvironment.

Keywords

paeoniflorin Chinese medicine gastric cancer associated fibroblasts migration invasion 

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Notes

Author Contributions

Wang ZF, Ma DG and Jia YF contributed to the study design. Wang ZF, Wang L, Feng L and Fu JW performed the experiments. Li Y and Wang DT collected and analyzed the data. All authors read and approved the final version of the manuscript for publication.

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Copyright information

© The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Zhen-fei Wang
    • 1
  • Da-guang Ma
    • 1
  • Ling Wang
    • 2
  • Li Feng
    • 2
  • Jian-wei Fu
    • 3
  • Ying Li
    • 2
  • Dan-ting Wang
    • 2
  • Yong-feng Jia
    • 1
    Email author
  1. 1.The Laboratory for Tumor Molecular DiagnosisAffiliated People’s Hospital of Inner Mongolia Medical UniversityHohhotChina
  2. 2.Department of GastroenterologyAffiliated People’s Hospital of Inner Mongolia Medical UniversityHohhotChina
  3. 3.The Central Laboratory of People’ Hospital of Wuhai City, Inner Mongolia Autonomous RegionWuhaiChina

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