Synergy between PPARγ ligands and platinum-based drugs in cancer
Synergy between PPARγ ligands and platinum-based drugs in cancer
复制标题
DOI：
10.1016/j.ccr.2007.02.025
复制
发表时间：
2007-05-01
期刊：
影响因子：
50.3
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
--
作者：
Girnun, Geoffrey D.;Naseri, Elnaz;Spiegelman, Bruce M.
PPAR γ是核受体家族的成员，激动剂配体对其具有抗生长作用。然而，使用PPAR γ配体作为单一疗法的临床研究未能显示有益效果。在这里，我们研究了目前用于特定癌症的化疗药物对PPAR γ激活的影响。我们观察到罗格列酮和铂类药物在几种不同的癌症中具有惊人的协同作用，无论是在体外还是使用可移植的和化学诱导的“自发性”肿瘤模型。这种作用似乎部分是由于金属硫蛋白（已被证明参与铂类药物治疗耐药性的蛋白质）的PPAR γ介导的下调。这些数据有力地表明，将PPAR γ激动剂和铂类药物组合用于治疗某些人类癌症。
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.