a novel therapeutic strategy for the treatment of glioma, combining chemical and molecular targeting of hsp90a一种新型治疗脑胶质瘤的治疗策略,结合hsp90a的化学和分子定位.pdfVIP

Cancers 2011, 3, 4228-4244; doi:10.3390/cancers3044228 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Article A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90 Adi Mehta, Leroy Shervington, Chinmay Munje and Amal Shervington * Brain Tumour North West, Faculty of Science and Technology, University of Central Lancashire, Preston, PR1 2HE, UK; E-Mails: abmehta@uclan.ac.uk (A.M.); lashervington@uclan.ac.uk (L.S.); crmunje@uclan.ac.uk (C.M.) * Author to whom correspondence should be addressed; E-Mail: aashervington@; Tel.: +44-0-1772893519; Fax: +44-0-1772892929. Received: 21 October 2011; in revised form: 21 November 2011 / Accepted: 30 November 2011 / Published: 8 December 2011 Abstract: Hsp90’s vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90 was downregulated using the post-transcriptional RNAi strategy (sihsp90) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90, 17-AAG and concurrent sihsp90/17-AAG (combined treatment). Both Hsp90 gene silencing and the protein inhibitor approaches resulted in a dramati