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Transcription profiling of human A540 non small cell carcinoma cell lines reveals synergy between PPARgamma ligands and platinum-based drugs in cancer


ABSTRACT: PPARγ is a member of the nuclear receptor family for which agonist ligands have anti-growth 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 Experiment Overall Design: Cells were treated with either DMSO/control, rosiglitazone, carboplatin or combination or rosiglitazone and carboplatin in duplicate for 24 hr. RNA was isolated and microarray analysis carried out by the Dana-Farber Cancer Institute Microarray Core.

ORGANISM(S): Homo sapiens

SUBMITTER: Geoffrey Girnun 

PROVIDER: E-GEOD-7035 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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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