过氧化物酶体增殖物激活受体γ（PPARγ）配体与铂类药物在癌症治疗中的协同作用。
Synergy between PPARgamma ligands and platinum-based drugs in cancer.
作者信息
Girnun Geoffrey D, Naseri Elnaz, Vafai Scott B, Qu Lishu, Szwaya Jeffrey D, Bronson Roderick, Alberta John A, Spiegelman Bruce M
机构信息
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Cancer Cell. 2007 May;11(5):395-406. doi: 10.1016/j.ccr.2007.02.025.
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.
摘要
过氧化物酶体增殖物激活受体γ（PPARγ）是核受体家族的成员，其激动剂配体具有抗生长作用。然而，将PPARγ配体作为单一疗法的临床研究未能显示出有益效果。在此，我们研究了当前用于特定癌症的化疗药物激活PPARγ的效果。我们观察到，在体外以及使用可移植和化学诱导的“自发”肿瘤模型时，罗格列酮与铂类药物在几种不同癌症中均表现出显著的协同作用。这种效应似乎部分归因于PPARγ介导的金属硫蛋白下调，金属硫蛋白已被证明与铂类疗法的耐药性有关。这些数据强烈表明，联合使用PPARγ激动剂和铂类药物治疗某些人类癌症。
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