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