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Combination of hyperthermia and bortezomib results in additive killing in mantle cell lymphoma cells.
Int. J. Hyperthermia 25, 262-272 (2009)
The proteasome inhibitor bortezomib exhibits antitumor activity in many malignancies including mantle cell lymphoma (MCL). Unfortunately, many patients fail to respond to treatment or become refractory. Hyperthermia is an effective chemosensitizer that in combination with some chemotherapeutic agents has shown clinical activity in phase II and III studies. The aim of this study was to use MCL cell lines to investigate the potential benefit of combining clinically relevant doses of bortezomib with two different thermal doses (41.8 degrees C/120 min and 44 degrees C/30 min) that mimic the heterogeneity of the temperature distributions achieved within tumors during hyperthermia. Treated tumor cells were assessed for proliferation using the WST-1 assay and for apoptosis by annexin V staining, while heat shock protein (HSP) levels were determined following western blot analysis. Our results demonstrated that MCL cell lines that are sensitive to bortezomib are also thermosensitive and have low basal expression of hsp27, whereas the bortezomib-resistant MCL cell line strongly expresses hsp27 and is thermoresistant. Interestingly, pre-treatment of MCL cell lines with heat at the two different thermal doses, and the transient elevation of hsp27 and hsp70, do not impair their primary sensitivity to bortezomib. Finally, we show that the concurrent treatment of heat and bortezomib results in additive killing in MCL cell lines. In conclusion, these results suggest that the application of bortezomib, under thermal conditions, in mantle cell lymphoma cells may be beneficial and warrants further investigation.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Heat shock proteins; hyperthermia; proteasome inhibition; mantle cell lymphoma; proteasome inhibitor bortezomib; multiple-myeloma cells; non-hodgkins-lymphoma; heat-shock response; phase-ii; cancer-cells; molecular chaperones; tumor-cells; expression; resistant
ISSN (print) / ISBN
0265-6736
e-ISSN
1464-5157
Quellenangaben
Volume: 25,
Issue: 4,
Pages: 262-272
Publisher
Informa Healthcare
Non-patent literature
Publications
Reviewing status
Peer reviewed