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Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells.
- Source :
-
Cancer research [Cancer Res] 2003 Oct 01; Vol. 63 (19), pp. 6174-7. - Publication Year :
- 2003
-
Abstract
- Bortezomib (PS-341), a selective inhibitor of proteasome, induces apoptosis in various tumor cells, but its mechanism of action is unclear. Treatment with PS-341 induces apoptosis in SUDHL6 (DHL6), but not SUDHL4 (DHL4), lymphoma cells. Microarray analysis shows high RNA levels of heat shock protein-27 (Hsp27) in DHL4 versus DHL6 cells, which correlates with Hsp27 protein expression. Blocking Hsp27 using an antisense strategy restores the apoptotic response to PS-341 in DHL4 cells; conversely, ectopic expression of wild-type Hsp27 renders PS-341-sensitive DHL6 cells resistant to PS-341. These findings provide the first evidence that Hsp27 confers PS-341 resistance.
- Subjects :
- Apoptosis drug effects
Bortezomib
Cell Line, Tumor
Cell Survival drug effects
Cysteine Endopeptidases
Drug Resistance, Neoplasm
HSP27 Heat-Shock Proteins
Humans
Leupeptins pharmacology
Lymphoma enzymology
Lymphoma genetics
Lymphoma pathology
Molecular Chaperones
Multienzyme Complexes antagonists & inhibitors
Neoplasm Proteins biosynthesis
Neoplasm Proteins genetics
Neoplasm Proteins physiology
Proteasome Endopeptidase Complex
RNA, Messenger genetics
RNA, Messenger metabolism
Transfection
Boronic Acids pharmacology
Heat-Shock Proteins
Lymphoma drug therapy
Neoplasm Proteins antagonists & inhibitors
Pyrazines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 63
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 14559800