Inhibition of constitutively activated Stat3 signaling pathway suppresses growth of prostate cancer cells

Zuyao Ni, Wei Lou, Eddy S. Leman, Allen C Gao

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

Overexpression of interleukin 6, a downstream target of the GEX2 homeobox gene, has been linked to the progression of prostate cancer. The Janus kinase-signal transducers and activators of transcription signaling pathway transmits interleukin 6-mediated signals from cell surface receptors to the target genes in the nucleus and is critical in mediating cellular growth and differentiation. We demonstrate the cells derived from both rat and human prostate cancers have constitutively activated Stat3, with Stat3 activation being correlated with malignant potential. Blockade of activated Stat3 by ectopic expression of a dominant-negative Stat3 in human prostate cancer cells significantly suppresses their growth in vitro and their tumorigenicity in vivo. Furthermore, the Janus kinase inhibitor, tyrphostin AG490, inhibited the constitutive activation of Stat3 and suppressed the growth of human prostate cancer cells. These results indicate that activation of Stat3 signaling is essential in the progression of prostate cancer cells and suggest that targeting Stat3 signaling may yield a potential therapeutic intervention for prostate cancer.

Original languageEnglish (US)
Pages (from-to)1225-1228
Number of pages4
JournalCancer Research
Volume60
Issue number5
StatePublished - Mar 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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