Synergy between PPARγ ligands and platinum-based drugs in cancer

被引：128

作者：

Girnun, Geoffrey D.

Naseri, Elnaz

Vafai, Scott B.

Qu, Lishu

Szwaya, Jeffrey D.

Bronson, Roderick

Alberta, John A.

Spiegelman, Bruce M. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

来源：

CANCER CELL | 2007年 / 11卷 / 05期

关键词：

D O I：

10.1016/j.ccr.2007.02.025

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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

引用

页码：395 / 406

页数：12

共 58 条

[1] EXPRESSION AND PURIFICATION OF THE LEUCINE ZIPPER AND DNA-BINDING DOMAINS OF FOS AND JUN - BOTH FOS AND JUN CONTACT DNA DIRECTLY [J].