Co-inhibition of HSP70/HSP90 synergistically sensitizes nasopharyngeal carcinoma cells to thermotherapy

Integr Cancer Ther. 2012 Mar;11(1):61-7. doi: 10.1177/1534735411399900. Epub 2011 Apr 15.

Abstract

The upregulation of both HSP70 and HSP90 frequently compromises the effects of thermotherapy. The co-inhibition of HSP70/HSP90 may be preferable to enhance the effects of thermotherapy on nasopharyngeal carcinoma cells. The changes of HSP70 and HSP90 were detected after thermotherapy in human nasopharyngeal cancer cell HNE1. 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) and quercetin were used to inhibit the activity of HSP90 and HSP70. The enhanced effects were evaluated in vitro and in vivo. Both HSP70 and HSP90 were upregulated promptly in HNE1 after thermotherapy. Single inhibition of HSP70 resulted in overexpression and delayed descent of HSP90. The co-inhibition of HSP70/HSP90 with quercetin plus 17-DMAG significantly increased apoptosis in hyperthermia-treated HNE1 cells both in vitro and in vivo. The co-inhibition of HSP70/HSP90 synergistically sensitizes nasopharyngeal carcinoma cells to hyperthermia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Benzoquinones / pharmacology*
  • Carcinoma
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Drug Synergism
  • HSP70 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Hyperthermia, Induced / methods*
  • Lactams, Macrocyclic / pharmacology*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy*
  • Quercetin / pharmacology*
  • Up-Regulation / drug effects

Substances

  • Benzoquinones
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin
  • Quercetin