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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Girnun GD,Naseri E,Vafai SB,Qu L,Szwaya JD,Bronson R,Alberta JA,Spiegelman BMdoi
10.1016/j.ccr.2007.02.025subject
Has Abstractpub_date
2007-05-01 00:00:00pages
395-406issue
5eissn
1535-6108issn
1878-3686pii
S1535-6108(07)00066-9journal_volume
11pub_type
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