PLoS ONE (Jan 2021)
Ruxolitinib with resminostat exert synergistic antitumor effects in Cutaneous T-cell Lymphoma.
Abstract
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.