期刊
CANCER LETTERS
卷 318, 期 2, 页码 145-153出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.09.043
关键词
Heat shock factor 1; Heat shock proteins; Heat shock response pathway; Triazole nucleoside; Pancreatic cancer
类别
资金
- National Mega Project on Major Drug Development [2009ZX09301-014]
- La Ligue Contre le Cancer [BL-8670]
- Wuhan University
- CNRS
- INSERM
- INSERM Transfert
- la Fondation pour la Recherche Medicale
- M.W. le program de bourses d'excellene d'Eiffel
- Y.F. the China Scholarship Council
Issued from a lead optimization process, we have identified a novel triazole nucleoside analog which elicits potent anticancer activity on drug-resistant pancreatic cancer. Most importantly, this compound targets heat shock response pathways by down-regulation of heat shock transcription factor 1 and consequential down-regulation of multiple heat shock proteins HSP27, HSP70 and HSP90. Down-regulation of these proteins caused the shut-down of several oncogenic pathways and caspase-dependent apoptosis resulting in a potent anticancer effect in vitro and in vivo. These results demonstrate the potential rewards gained in searching for anticancer candidates with multimodal actions on heat shock response pathways via HSF1 down-regulation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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