Inhibition of the mevalonate pathway potentiates the effects of lenalidomide in myeloma
| Autor: | Henk M. Lokhorst, Berris van Kessel, Niels W.C.J. van de Donk, Ellen van der Spek, Lijnie Bogers-Boer, Andries C. Bloem |
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| Rok vydání: | 2007 |
| Předmět: |
STAT3 Transcription Factor
Cancer Research Simvastatin Blotting Western Protein Prenylation Mevalonic Acid Antineoplastic Agents Apoptosis Pharmacology hemic and lymphatic diseases Cell Line Tumor polycyclic compounds medicine Humans In patient cardiovascular diseases Viability assay Lenalidomide Multiple myeloma Cell Proliferation Myeloma cell business.industry nutritional and metabolic diseases Drug Synergism Hematology medicine.disease Thalidomide Oncology Cancer research lipids (amino acids peptides and proteins) Mevalonate pathway business Multiple Myeloma medicine.drug |
| Zdroj: | Leukemia research. 33(1) |
| ISSN: | 0145-2126 |
| Popis: | The effects of the combination of simvastatin and lenalidomide were analyzed in myeloma. Myeloma cell lines and patient myeloma cells were incubated with different concentrations of lenalidomide, simvastatin, or the combination. Co exposure to simvastatin and lenalidomide resulted in a synergistic reduction of cell viability in myeloma cells. This effect was due to induction of apoptosis and inhibition of proliferation. The combination augmented induction of caspase-8 cleavage and enhanced down-regulation of pStat3. Mevalonate and GGOH abrogated the synergy between lenalidomide and simvastatin. These data provide a rationale for the clinical evaluation of lenalidomide and simvastatin in patients with myeloma. |
| Databáze: | OpenAIRE |
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