TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000264657
  • Gene Name:STAT3
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:IL?6/JAK2/STAT3 signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:Tyrphostin B42
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:pancreatic cancer
  • Tissue:tissues

Other information

  • Title:Tyrphostin B42 attenuates trichostatin A-mediated resistance in pancreatic cancer cells by antagonizing IL-6/JAK2/STAT3 signaling
  • Journal:Oncology Reports
  • Published:2018
  • PubMed ID:29393444
  • Abstract:Drug-resistance is the key reason for the ineffectiveness of chemotherapy in pancreatic cancer. Thus, it is very important to explore the molecular mechanisms of drug-resistance and the methods of effective intervention. In the present study, we investigated the effect of tyrphostin B42, also called AG490, on histone deacetylase (HDAC) inhibitor trichostatin A (TSA)-induced resistance in pancreatic cancer cells (PCCs). Evidence from phase contrast microscope revealed that TSA-resistant cells (PANC-1-TSA) had higher proliferative activity than non-resistant cells (PANC-1). This over-proliferative activity induced by TSA may be associated with abnormal activation of JAK2/STAT3 signaling, which can be strengthened by interleukin-6 (IL-6), a STAT3-upstream inducer, resulting in enhanced expression of STAT3-downstream target genes including c-Myc, c-Src, HIF-1α, and CCND1. In addition, increased expression of Bcl-2 mRNA and decreased expression of Bax mRNA in PANC-1-TSA cells indicated that TSA induced the inhibition of mitochondrial-dependent apoptosis in PCCs. Tyrphostin B42 treatment evidently antagonized the activation of IL-6/JAK2/STAT3 in a dose-dependent manner. As a result, tyrphostin B42 inhibited the over-proliferative activity of PANC-1-TSA cells, and downregulated the expression of IL-6/JAK2/STAT3-downstream target genes. Moreover, tyrphostin B42 induced the apoptosis of PCCs by regulating the expression of mitochondrial-related genes. Therefore, these findings demonstrated that tyrphostin B42 attenuated TSA-mediated resistance in PCCs by antagonizing the IL-6/JAK2/STAT3 signaling.
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