Triptolide enhances the sensitivity of multiple myeloma cells to dexamethasone via microRNAs

Leuk Lymphoma. 2012 Jun;53(6):1188-95. doi: 10.3109/10428194.2011.638069. Epub 2012 Feb 13.

Abstract

Recently triptolide (TPL) has been proved to have the capacity to inhibit the proliferation of multiple myeloma (MM) cells as well as leukemic cells in vitro. In the present study, we found a synergistic effect when TPL was added to dexamethasone to induce apoptosis in MM.1S cells. This combination induced a significantly higher proportion of apoptotic cells compared with those treated with each drug separately. TPL down-regulated the expression of miR142 - 5p and miR181a, which have been shown to inhibit glucocorticoid receptor (GR) expression. MicroRNA mimics and inhibitors inhibited or enhanced the synergistic effect between TPL and dexamethasone in inducing apoptosis in MM.1S cells, suggesting an important role of miR142 - 5p and miR181a in GR regulation by TPL. The in vitro proapoptotic effect of TPL associated with dexamethasone reveals a new lead for further clinical investigation into the treatment of patients with MM with TPL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology*
  • Diterpenes / administration & dosage
  • Diterpenes / pharmacology*
  • Drug Evaluation, Preclinical
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Drug Synergism
  • Epoxy Compounds / administration & dosage
  • Epoxy Compounds / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / pathology
  • Phenanthrenes / administration & dosage
  • Phenanthrenes / pharmacology*

Substances

  • Diterpenes
  • Epoxy Compounds
  • MicroRNAs
  • Phenanthrenes
  • triptolide
  • Dexamethasone