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Cancer Lett. 2013 Dec 1;341(2):224-30. doi: 10.1016/j.canlet.2013.08.009. Epub 2013 Aug 11.

Tumoricidal effects of the JAK inhibitor Ruxolitinib (INC424) on hepatocellular carcinoma in vitro.

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  • 1Storr Liver Unit, Westmead Millennium Institute, the University of Sydney at the Westmead Hospital, Westmead, NSW 2145, Australia.

Abstract

Hepatocellular carcinoma (HCC) is an aggressive tumour with limited treatment options. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling pathway plays a key role in promoting tumorigenesis in HCC. Recently a new JAK inhibitor Ruxolitinib (INC424) has been developed by Novartis Pharmaceuticals and it shows high affinity for JAK signalling with very low affinity for non-JAK targets. Clinical trials have demonstrated that Ruxolitinib has good therapeutic efficacy for the treatment of myelofibrosis and is currently FDA approved for the treatment of advanced stages of this disease. Our study tested the effects of Ruxolitinib on HCC tumorigenesis in vitro. Ruxolitinib effectively inhibited JAK/STAT signalling in HCC cells with a significant reduction in the expression of JAK downstream targets pSTAT1 and pSTAT3. Ruxolitinib also caused a marked reduction in the proliferation and colony formation of HCC cells. The antiproliferative effect of Ruxolitinib on HCC cells is unlikely due to off-target effects with no inhibition of key regulators of other cell proliferative pathways. To our knowledge this study is the first to report on the effect of Ruxolitinib on liver cancer cells.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

HCC; Hepatocellular carcinoma; INC424; JAK signalling; Ruxolitinib; Ruxolitinib (INC018424); hepatocellular carcinoma

PMID:
23941832
[PubMed - indexed for MEDLINE]
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