Interleukin-6 and JAK2/STAT3 signaling mediate the reversion of dexamethasone resistance after dexamethasone withdrawal in 7TD1 multiple myeloma cells

Leuk Res. 2013 Oct;37(10):1322-8. doi: 10.1016/j.leukres.2013.06.026. Epub 2013 Jul 18.

Abstract

We previously reported the establishment and characteristics of a DXM-resistant cell line (7TD1-DXM) generated from the IL6-dependent mouse B cell hybridoma, 7TD1 cell line. After withdrawing DXM from 7TD1-DXM cells over 90 days, DXM significantly inhibited the cell growth and induced apoptosis in the cells (7TD1-WD) compared with 7TD1-DXM cells. Additionally, IL-6 reversed while IL-6 antibody and AG490 enhanced the effects of growth inhibition and apoptosis induced by DXM in 7TD1-WD cells. Our study demonstrates that 7TD1-DXM cells become resensitized to DXM after DXM withdrawal, and IL-6 and JAK2/STAT3 pathways may regulate the phenomenon.

Keywords: AG490; Dexamethasone resistance; Dexamethasone withdrawal; Interleukin-6; JAK2/STAT3 signaling pathway; Multiple myeloma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dexamethasone / pharmacology*
  • Dexamethasone / toxicity
  • Drug Resistance, Neoplasm*
  • Interleukin-6 / pharmacology*
  • Janus Kinase 2 / metabolism*
  • Mice
  • Multiple Myeloma / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*
  • Tyrphostins / pharmacology

Substances

  • Antineoplastic Agents
  • Interleukin-6
  • STAT3 Transcription Factor
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Dexamethasone
  • Janus Kinase 2