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Inhibitory effect and mechanism of mesenchymal stem cells on melanoma cells

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Abstract

Purpose

To explore the inhibitory effect and mechanism of MSCs on melanoma proliferation.

Methods

The inhibitory effect of MSCs on melanoma A375 cells was detected by co-culture and conditioned medium (CM) experiments using MTT method. The cell cycle was analyzed by flow cytometry. Then, Western Blot experiment detected the expression of proteins related to NF-κB signaling in A375 cells. The expression of IL-1Ra in MSCs was proved by RT-PCR. The over-expression and silencing vector pcDNA3.1-EGFP-IL-1Ra and pGPH1-IL-1R were constructed and transfected into MSCs cells. After that, the changes of inhibitory effect and cell cycle from MSCs-S and MSCs-O CM on A375 cells were explored. The expression of proteins related to NF-κB signaling in A375 cells after MSCs-S or MSCs-O CM treatment was detected by Western Blot. MSCs, MSCs-S, or MSCs-O and A375 cells were co-injected into nude mice under the arms, the growth of tumor was observed, the frozen sections were made, and H&E staining of tumor tissue was performed.

Results

The proliferation of A375 cells was inhibited and the cell cycle of A375 was arrested by MSCs. The expressions of cytokines related to NF-κB signaling were down-regulated. Over-expression and silence of Interleukin 1 receptor antagonist (IL-1Ra), specifically blocking activation of NF-κB signaling, indicated that inhibitory effect from MSCs was enhanced or weakened respectively, which suggested that IL-1Ra was involved in the inhibitory effect. In vivo, tumor initiation and growth were significantly inhibited when A375 cells were co-injected with MSCs into nude mice, which were related to the expression level of IL-1Ra.

Conclusion

MSCs could inhibit the proliferation and tumor initiation of melanoma A375 cells through NF-κB signaling. MSCs could secret IL-1Ra and inhibit expressions of NF-κB signaling-related factors of tumor cells, and cause cell cycle arrest in G1 phase.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81201762) and the National High Technology Research and Development Program (863 Program) of China (2014AA021605).

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Author notes

  1. J. Zhang and L. Hou contributed equally to this work.

Authors and Affiliations

  1. College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, People’s Republic of China

    J. Zhang, L. Hou, D. Zhao, M. Pan, Z. Wang, H. Hu & J. He

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  1. J. Zhang
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  2. L. Hou
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Correspondence to L. Hou.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Zhang, J., Hou, L., Zhao, D. et al. Inhibitory effect and mechanism of mesenchymal stem cells on melanoma cells. Clin Transl Oncol 19, 1358–1374 (2017). https://doi.org/10.1007/s12094-017-1677-3

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