Can hsp90alpha-targeted siRNA combined with TMZ be a future therapy for glioma?

Cancer Invest. 2010 Jul;28(6):608-14. doi: 10.3109/07357901003630967.

Abstract

Hsp90alpha's vital role in cell cycle progression and apoptosis together with its presence in gliomas and absence in normal tissue, make it a credible target for cancer therapy. Three sets of dsRNA oligos designed to align different regions of the hsp90alpha sequence were used to downregulate hsp90alpha. SiRNA 1, 2, and 3 resulted in significant levels of silencing of hsp90alpha after 48 hr treatment (p < .0001). Concurrent treatment of the glioma cell line U87-MG with siRNA 1 and temozolomide (TMZ) resulted in a 13-fold reduction in the dose of TMZ required to achieve a similar effect if TMZ was used alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemotherapy, Adjuvant
  • Cisplatin / pharmacology
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy / methods*
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology
  • Glioma / therapy*
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Inhibitory Concentration 50
  • RNA Interference*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism*
  • Temozolomide
  • Time Factors
  • Transfection

Substances

  • Antineoplastic Agents, Alkylating
  • HSP90 Heat-Shock Proteins
  • HSP90AA2P protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • Dacarbazine
  • Cisplatin
  • Temozolomide