Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel

Oncotarget. 2015 Mar 20;6(8):6386-405. doi: 10.18632/oncotarget.3443.


Persistent phosphorylation of signal transducers and activators of transcription 3 (STAT3) is frequently observed in tumor cells. We found that brassinin (BSN) suppressed both constitutive and IL-6-inducible STAT3 activation in lung cancer cells. Moreover, BSN induced PIAS-3 protein and mRNA, whereas the expression of SOCS-3 was reduced. Knockdown of PIAS-3 by small interfering RNA prevented inhibition of STAT3 and cytotoxicity by BSN. Overexpression of SOCS-3 in BSN-treated cells increased STAT3 phosphorylation and cell viability. BSN down-regulated STAT3-regulated gene products, inhibited proliferation, invasion, as well as induced apoptosis. Most importantly, when administered intraperitoneally, combination of BSN and paclitaxel significantly decreased the tumor development in a xenograft lung cancer mouse model associated with down-modulation of phospho-STAT3, Ki-67 and CD31. We suggest that BSN inhibits STAT3 signaling through modulation of PIAS-3 and SOCS-3, thereby attenuating tumor growth and increasing sensitivity to paclitaxel.

Keywords: PIAS-3; SOCS-3; STAT3; apoptosis; brassinin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Indoles / pharmacology*
  • K562 Cells
  • Male
  • Mice
  • Mice, Nude
  • Molecular Chaperones / metabolism*
  • Paclitaxel / pharmacology*
  • Protein Inhibitors of Activated STAT / metabolism*
  • Random Allocation
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / metabolism*
  • Thiocarbamates / pharmacology*
  • Transfection
  • Xenograft Model Antitumor Assays


  • Indoles
  • Molecular Chaperones
  • PIAS3 protein, human
  • Protein Inhibitors of Activated STAT
  • SOCS3 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Thiocarbamates
  • brassinin
  • Paclitaxel