STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells

Oncol Rep. 2017 Oct;38(4):2197-2204. doi: 10.3892/or.2017.5902. Epub 2017 Aug 11.

Abstract

Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes mediating cell survival, proliferation and angiogenesis and is aberrantly activated in various types of malignancies, including bladder cancer. We examined whether it could be a novel therapeutic target for bladder cancer using the STAT3 inhibitor WP1066. In T24 and UMUC-3 bladder cancer cells, 5 µM WP1066 prevented the phosphorylation of STAT3 and 2.5 µM WP1066 decreased cell survival and proliferation significantly (P<0.01). WP1066 also induced apoptosis accompanied by the suppression of the expression of Bcl-2 and Bcl-xL in T24 cells. Moreover, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased significantly (P<0.01) when cells were treated with WP1066. The activities of MMP-2 and MMP-9 were also decreased by treatment with 10 µM WP1066. Our results revealed that using WP1066 to inhibit the STAT3 signaling pathway suppressed the viability and invasiveness of bladder cancer cells effectively and could be a novel therapeutic strategy against bladder cancer.

MeSH terms

  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Pyridines / administration & dosage
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics*
  • Signal Transduction / drug effects
  • Tyrphostins / administration & dosage
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Pyridines
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tyrphostins
  • WP1066