Can hsp90alpha-targeted siRNA combined with TMZ be a future therapy for glioma?
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.
Cruickshanks
Nichola
N
Brain Tumour North West, Faculty of Science and Technology, University of Central Lancashire, Preston, United Kingdom.
Shervington
Leroy
L
Patel
Rahima
R
Munje
Chinmay
C
Thakkar
Dipti
D
Shervington
Amal
A
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
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