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Niclosamide and Pyrvinium Are Both Potential Therapeutics for Osteosarcoma, Inhibiting Wnt-Axin2-Snail Cascade

Young Yi1, Young Mi Woo2, Kyu Ho Hwang2

  • 1Department of Orthopedics, Inje University Seoul Paik Hospital, Seoul 04551, Korea.

Cancers
|September 28, 2021
PubMed

Insights

Anthelmintic agents niclosamide and pyrvinium suppress osteosarcoma (bone cancer) cell migration by inhibiting the Wnt/Snail pathway. These drugs target Axin2, offering potential new treatments for osteosarcoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma is a primary bone cancer with poor prognosis, especially in metastatic or recurrent cases.
  • Epithelial-mesenchymal transition (EMT), driven by Wnt signaling, promotes cancer cell invasion and metastasis.
  • The Wnt/Snail axis is implicated in osteosarcoma progression, but therapeutic targets remain elusive.

Purpose of the Study:

  • To investigate the therapeutic effects and regulatory mechanisms of niclosamide and pyrvinium in osteosarcoma.
  • To identify the role of Axin2 and Snail in osteosarcoma progression and metastasis.

Main Methods:

  • Utilized osteosarcoma cell lines and patient samples.
  • Administered niclosamide and pyrvinium to assess their impact on cellular mechanisms.
  • Measured cell migration and analyzed the Wnt/Snail signaling pathway and Axin2 expression.

Main Results:

  • Niclosamide and pyrvinium were found to target Axin2 in osteosarcoma cells.
  • These agents suppressed EMT by inhibiting the Wnt/Snail axis.
  • Axin2 and Snail were notably abundant in osteosarcoma samples.
  • Niclosamide and pyrvinium inhibited osteosarcoma cell migration at nanomolar concentrations.

Conclusions:

  • Axin2 and Snail are potential therapeutic targets for osteosarcoma.
  • Anthelmintic agents niclosamide and pyrvinium demonstrate therapeutic potential for osteosarcoma treatment.
Keywords:
Axin2SnailWntepithelial–mesenchymal transitionniclosamideosteosarcomapyrvinium

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