TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000369026
  • Gene Name:MCL1
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:RT-PCR
  • mRNA Pathway:apoptotic signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00398 (APRD01304, DB07438)
  • Drug Name:Sorafenib
  • Drug Method:down-regulated the gene expression the gene expression

Disease basic infommation

  • Disease:cholangiocarcinoma
  • Tissue:cell lines (HuCCT-1,15 KMCH-1,16 Mz-ChA-1,17 ,TFK-1)

Other information

  • Title:Sorafenib inhibits signal transducer and activator of transcription-3 signaling in cholangiocarcinoma cells by activating the phosphatase shatterproof 2
  • Journal:Hepatology
  • Published:2009
  • PubMed ID:19821497
  • Abstract:The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is one of the key signaling cascades in cholangiocarcinoma (CCA) cells, mediating their resistance to apoptosis. Our aim was to ascertain if sorafenib, a multikinase inhibitor, may also inhibit JAK/STAT signaling and, therefore, be efficacious for CCA. Sorafenib treatment of three human CCA cell lines resulted in Tyr(705) phospho-STAT3 dephosphorylation. Similar results were obtained with the Raf-kinase inhibitor ZM336372, suggesting sorafenib promotes Tyr(705) phospho-STAT3 dephosphorylation by inhibiting Raf-kinase activity. Sorafenib treatment enhanced an activating phosphorylation of the phosphatase SHP2. Consistent with this observation, small interfering RNA-mediated knockdown of phosphatase shatterproof 2 (SHP2) inhibited sorafenib-induced Tyr(705) phospho-STAT3 dephosphorylation. Sorafenib treatment also decreased the expression of Mcl-1 messenger RNA and protein, a STAT3 transcriptional target, as well as sensitizing CCA cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. In an orthotopic, syngeneic CCA model in rats, sorafenib displayed significant tumor suppression resulting in a survival benefit for treated animals. In this in vivo model, sorafenib also decreased tumor Tyr(705) STAT3 phosphorylation and increased tumor cell apoptosis.
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