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Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment

  • Authors:
    • Yuko Tanaka
    • Seiichi Okabe
    • Kazuma Ohyashiki
    • Akihiko Gotoh
  • View Affiliations / Copyright

    Affiliations: Division of Hematology, Tokyo Medical University, Tokyo 160‑0023, Japan
    Copyright: © Tanaka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 111
    |
    Published online on: February 8, 2022
       https://doi.org/10.3892/ol.2022.13231
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Abstract

Sphingosine 1‑phosphate (S1P) is a bioactive lipid involved in cancer progression through its binding to S1P receptors (S1PRs). However, the association between multiple myeloma (MM) and S1P is unclear. The current study aimed to investigate the potential anti‑cancer effects of fingolimod and sphingosine kinase (SK) inhibitors in myeloma cells and the effects of S1P‑induced chemoresistance and neovascularization on MM cell proliferation. MM cell lines were treated with the S1PR1 antagonist fingolimod and the SK inhibitors ABC294640 and SK1‑I, after which cell proliferation was measured. Protein expression was also assessed under each condition using immunoblotting. Serum S1P levels in patients with MM, monoclonal gammopathy of undetermined significance and healthy volunteers were assessed. Human umbilical vessel cells (HUVECs) were co‑cultured with anti‑S1P agents to assess the effect on cell migration. All treatments suppressed myeloma cell proliferation and caspase‑3‑mediated apoptosis by suppressing S1P activity. These findings suggest that S1P activation is associated with proliferation and survival for MM cells. S1P attenuated the proteosome inhibitor (PI) effect, while the anti‑S1P agents recovered the effect. In addition, S1P promoted the migration and proliferation of HUVECs, whereas the S1P inhibitors reduced the influence of S1P. This study highlights the therapeutic potential of anti‑S1P agents for MM treatment. Inhibition of S1P function may overcome resistance to PI developed by myeloma cells and inhibit the changes to the bone marrow microenvironment via neovascularization.
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Copy and paste a formatted citation
Spandidos Publications style
Tanaka Y, Okabe S, Ohyashiki K and Gotoh A: Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment. Oncol Lett 23: 111, 2022.
APA
Tanaka, Y., Okabe, S., Ohyashiki, K., & Gotoh, A. (2022). Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment. Oncology Letters, 23, 111. https://doi.org/10.3892/ol.2022.13231
MLA
Tanaka, Y., Okabe, S., Ohyashiki, K., Gotoh, A."Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment". Oncology Letters 23.4 (2022): 111.
Chicago
Tanaka, Y., Okabe, S., Ohyashiki, K., Gotoh, A."Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment". Oncology Letters 23, no. 4 (2022): 111. https://doi.org/10.3892/ol.2022.13231
Copy and paste a formatted citation
x
Spandidos Publications style
Tanaka Y, Okabe S, Ohyashiki K and Gotoh A: Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment. Oncol Lett 23: 111, 2022.
APA
Tanaka, Y., Okabe, S., Ohyashiki, K., & Gotoh, A. (2022). Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment. Oncology Letters, 23, 111. https://doi.org/10.3892/ol.2022.13231
MLA
Tanaka, Y., Okabe, S., Ohyashiki, K., Gotoh, A."Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment". Oncology Letters 23.4 (2022): 111.
Chicago
Tanaka, Y., Okabe, S., Ohyashiki, K., Gotoh, A."Potential of a sphingosine 1‑phosphate receptor antagonist and sphingosine kinase inhibitors as targets for multiple myeloma treatment". Oncology Letters 23, no. 4 (2022): 111. https://doi.org/10.3892/ol.2022.13231
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