Department of Clinical Laboratory Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan.
PPAR Res. 2012;2012:483656. doi: 10.1155/2012/483656. Epub 2012 May 21.
Peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RARs), members of the nuclear receptor superfamily, are transcription factors that regulate a variety of important cellular functions. PPARs form heterodimers retinoid X receptor (RXR), an obligate heterodimeric partner for other nuclear receptors. Several novel links between retinoid metabolism and PPAR responses have been identified, and activation of PPAR/RXR expression has been shown to increase response to retinoids. PPARγ has emerged as a key regulator of cell growth and survival, whose activity is modulated by a number of synthetic and natural ligands. While clinical trials in cancer patients with thiazolidinediones (TZD) have been disappointing, novel structurally different PPARγ ligands, including triterpenoids, have entered clinical arena as therapeutic agents for epithelial and hematopoietic malignancies. Here we shall review the antitumor advances of PPARγ, alone and in combination with RARα ligands in control of cell proliferation, differentiation, and apoptosis and their potential therapeutic applications in hematological malignancies.
过氧化物酶体增殖物激活受体 (PPARs) 和维甲酸受体 (RARs) 是核受体超家族的成员，它们是调节多种重要细胞功能的转录因子。PPARs 形成异二聚体维甲酸 X 受体 (RXR)，是其他核受体必需的异二聚体伴侣。已经确定了几种新的视黄酸代谢与 PPAR 反应之间的联系，并且已经表明激活 PPAR/RXR 表达会增加对视黄酸的反应。PPARγ 已成为细胞生长和存活的关键调节剂，其活性受许多合成和天然配体的调节。虽然在癌症患者中使用噻唑烷二酮类药物 (TZD) 的临床试验令人失望，但新型结构不同的 PPARγ 配体，包括三萜类化合物，已作为治疗上皮和造血恶性肿瘤的治疗剂进入临床领域。在这里，我们将回顾 PPARγ 的抗肿瘤进展，单独使用和与 RARα 配体联合使用以控制细胞增殖、分化和凋亡，以及它们在血液恶性肿瘤中的潜在治疗应用。
