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Synergy between PPARgamma ligands and platinum-based drugs in cancer.


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

SUBMITTER: Girnun GD 

PROVIDER: S-EPMC2564847 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Synergy between PPARgamma ligands and platinum-based drugs in cancer.

Girnun Geoffrey D GD   Naseri Elnaz E   Vafai Scott B SB   Qu Lishu L   Szwaya Jeffrey D JD   Bronson Roderick R   Alberta John A JA   Spiegelman Bruce M BM  

Cancer cell 20070501 5


PPARgamma is a member of the nuclear receptor family for which agonist ligands have antigrowth effects. However, clinical studies using PPARgamma ligands as a monotherapy failed to show a beneficial effect. Here we have studied the effects of PPARgamma 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 "  ...[more]

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