Journal
CANCER CELL
Volume 11, Issue 5, Pages 395-406Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2007.02.025
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Funding
- NIDDK NIH HHS [R37 DK031405-25, R01 DK057670-05, K01 DK064685, K01 DK064685-04, R37 DK 31405, R01 DK 57670, DK 064685, R01 DK057670, R37 DK031405] Funding Source: Medline
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PPAR gamma is a member of the nuclear receptor family for which agonist ligands have antigrowth effects. However, clinical studies using PPAR gamma ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPAR gamma activation with chemotherapeutic agents in current use for specific cancers. We observed a striking synergy between rosiglitazone and platinum-based drugs in several different cancers both in vitro and using transplantable and chemically induced spontaneous tumor models. The effect appears to be due in part to PPAR gamma-mediated downregulation of metallothioneins, proteins that have been shown to be involved in resistance to platinum-based therapy. These data strongly suggest combining PPAR gamma agonists and platinum-based drugs for the treatment of certain human cancers.
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