Synergy between PPARγ ligands and platinum-based drugs in cancer

被引：125
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
收藏
页码：395 / 406
页数：12
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