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

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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.

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Authors and Affiliations

  1. The Laboratory for Tumor Molecular Diagnosis, Affiliated People’s Hospital of Inner Mongolia Medical University, Hohhot, 010020, China

    Zhen-fei Wang, Da-guang Ma & Yong-feng Jia

  2. Department of Gastroenterology, Affiliated People’s Hospital of Inner Mongolia Medical University, Hohhot, 010020, China

    Ling Wang, Li Feng, Ying Li & Dan-ting Wang

  3. The Central Laboratory of People’ Hospital of Wuhai City, Inner Mongolia Autonomous Region, Wuhai, 016000, China

    Jian-wei Fu

Authors
  1. Zhen-fei Wang
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  2. Da-guang Ma
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  3. Ling Wang
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  4. Li Feng
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  5. Jian-wei Fu
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  6. Ying Li
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  7. Dan-ting Wang
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  8. Yong-feng Jia
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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.

Corresponding author

Correspondence to Yong-feng Jia.

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Conflict of Interest

There is no conflict of interest in this study

Supported by the National Natural Science Foundation of China (No. 81760552), the Inner Mongolia Natural Science Foundation (No. 2016MS0824), the Outstanding Youth in Science and Technology of Inner Mongolia Autonomous Region Universities (No. NJYT-17-B30), and the Technology Million Project of Inner Mongolia Medical University (No. YKD2015KJBW008), China

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Wang, Zf., Ma, Dg., Wang, L. et al. Paeoniflorin Inhibits Migration- and Invasion-Promoting Capacities of Gastric Cancer Associated Fibroblasts. Chin. J. Integr. Med. 25, 837–844 (2019). https://doi.org/10.1007/s11655-018-2985-3

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  • DOI: https://doi.org/10.1007/s11655-018-2985-3

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