PLoS ONE (Jan 2021)

Ruxolitinib with resminostat exert synergistic antitumor effects in Cutaneous T-cell Lymphoma.

  • Fani Karagianni,
  • Christina Piperi,
  • Vassiliki Mpakou,
  • Aris Spathis,
  • Periklis G Foukas,
  • Maria Dalamaga,
  • Vasiliki Pappa,
  • Evangelia Papadavid

DOI
https://doi.org/10.1371/journal.pone.0248298
Journal volume & issue
Vol. 16, no. 3
p. e0248298

Abstract

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BackgroundThe combination of JAK/STAT and HDAC inhibitors exerted beneficial effects in haematological malignancies, presenting promising therapeutic CTCL targets. We aim to investigate the efficacy of JAK1/2i ruxolitinib in combination with HDACi resminostat in CTCL in vitro.Material & methodsNon-toxic concentrations of ruxolitinib and/or resminostat were administered to MyLa (MF) and SeAx (SS) cells for 24h. Cytotoxicity, cell proliferation and apoptosis were estimated through MTT, BrdU/7AAD and Annexin V/PI assay. Multi-pathway analysis was performed to investigate the effect of JAK1/2i and/or HDACi on JAK/STAT, Akt/mTOR and MAPK signalling pathways.ResultsBoth drugs and their combination were cytotoxic in MyLa (pConclusionThe JAKi/HDACi combination exhibited substantial anti-tumor effects in CTCL cell lines, and may represent a promising novel therapeutic modality for CTCL patients.