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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Girnun GD,Naseri E,Vafai SB,Qu L,Szwaya JD,Bronson R,Alberta JA,Spiegelman BM

doi

10.1016/j.ccr.2007.02.025

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

395-406

issue

5

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(07)00066-9

journal_volume

11

pub_type

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