Cancer Cell
Volume 11, Issue 5, 8 May 2007, Pages 395-406
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Article
Synergy between PPARγ Ligands and Platinum-Based Drugs in Cancer

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Summary

PPARγ is a member of the nuclear receptor family for which agonist ligands have antigrowth effects. However, clinical studies using PPARγ ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPARγ 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 PPARγ-mediated downregulation of metallothioneins, proteins that have been shown to be involved in resistance to platinum-based therapy. These data strongly suggest combining PPARγ agonists and platinum-based drugs for the treatment of certain human cancers.

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