HSP90 als Therapie-Target bei Gemcitabine und 5-Fluorouracil resistentem Pankreaskarzinom
作者： J.L. Rabofski , Y.K. Vashist , T. Kalinina , C. Guengor , J.R. Izbicki
DOI: 10.1007/978-3-642-12192-0_26
关键词: Hsp90 、 Geldanamycin 、 Fluorouracil 、 Chemistry 、 Protein kinase B 、 Immunology 、 Cancer research 、 Pancreatic cancer 、 Gemcitabine 、 Chemotherapy 、 Apoptosis
摘要: Gemcitabine and 5- Fluorouracil (5-FU) are currently the standard of care in metastatic adjuvant setting pancreatic cancer (PC). However, overall survival has reached a plateau since PC inherits major potential intrinsic acquired resistance to chemotherapy. Molecular profile is characterized by many client proteins (CP) HSP90. Functional inhibition HSP90 Geldanamycin leads simultaneous proteosomal degradation multiple CP. Aim study was evaluate efficacy HSP90-inhibitors 5-FU resistant PC. Human cell lines (PaCa5061, PaCa5072 PaCa5156) were isolated brought culture. The anti-proliferative effect different (17AAG, 17DMAG 17AEPGA) evaluated MTT-Assay. changes apoptosis shown Western-blot (WB) analysis. All tested 5-FU. 17AAG water soluble derivates 17AEPGA showed high activity all with IC50 < 1 μM. A significant down regulation EGFR, IGF-1R, AKT MAPK demonstrated WB initiation as an early event proven CASPASE-3 PARP staining WB. Our data demonstrate that promising target
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sci-hub.st 参考文章(3)
D Mahalingam, R Swords, J S Carew, S T Nawrocki, K Bhalla, F J Giles, Targeting HSP90 for cancer therapy British Journal of Cancer. ,vol. 100, pp. 1523- 1529 ,(2009) , 10.1038/SJ.BJC.6605066
Adeela Kamal, Lia Thao, John Sensintaffar, Lin Zhang, Marcus F. Boehm, Lawrence C. Fritz, Francis J. Burrows, A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors Nature. ,vol. 425, pp. 407- 410 ,(2003) , 10.1038/NATURE01913
Ghassan El Maalouf, Christophe Le Tourneau, Georges Nicolas Batty, Sandrine Faivre, Eric Raymond, Markers involved in resistance to cytotoxics and targeted therapeutics in pancreatic cancer Cancer Treatment Reviews. ,vol. 35, pp. 167- 174 ,(2009) , 10.1016/J.CTRV.2008.10.002