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

Wilson, George S., Tian, Aiping, Hebbard, Lionel, Duan, Wei, George, Jacob, Li, Xun, and Qiao, Liang (2013) Tumoricidal effects of the JAK inhibitor Ruxolitinib (INC424) on hepatocellular carcinoma in vitro. Cancer letters, 341 (2). pp. 224-230.

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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.

Item ID: 40180
Item Type: Article (Research - C1)
ISSN: 1872-7980
Keywords: ruxolitinib; hepatocellular carcinoma; JAK signalling
Funders: NSW Cancer Institute, National Health and Medical Research Council (NHMRC), Robert W. Storr bequest to the Sydney Medical Foundation, Chinese Academy of Sciences (CAS)
Projects and Grants: NHMRC grant APP1006200, NHMRC grant APP1047417, CAS “Western Light” Talents Training Program
Date Deposited: 27 Aug 2015 01:08
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
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