title: Can hsp90alpha-targeted siRNA combined with TMZ be a future therapy for glioma?
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.
authors.affiliation: Brain Tumour North West, Faculty of Science and Technology, University of Central Lancashire, Preston, United Kingdom.
authors.forename: Nichola
authors.initials: N
authors.lastname: Cruickshanks
authors.forename: Leroy
authors.initials: L
authors.lastname: Shervington
authors.forename: Rahima
authors.initials: R
authors.lastname: Patel
authors.forename: Chinmay
authors.initials: C
authors.lastname: Munje
authors.forename: Dipti
authors.initials: D
authors.lastname: Thakkar
authors.forename: Amal
authors.initials: A
authors.lastname: Shervington
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000494:pharmacology; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D000077204:Temozolomide; D013997:Time Factors; D014162:Transfection
chemical_list: D018906:Antineoplastic Agents, Alkylating; D018841:HSP90 Heat-Shock Proteins; C533585:HSP90AA2P protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide