文章：

过氧化物酶体增殖物激活受体与癌症：复杂的故事

Peroxisome-proliferator-activated receptors and cancers: complex stories

原文发布日期：2004-01-01

DOI: 10.1038/nrc1254

类型: Review Article

开放获取: 否

要点：

1. Peroxisome-proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear-hormone-receptor family. Three isotypes have been identified — PPARα, PPARβ/δ and PPARγ.
2. PPARs are activated by endogenous ligands — fatty acids and fatty-acid derivatives, for which they act as intracellular sensors — which leads to transcriptional regulation of pathways that are involved in lipid and glucose metabolism.
3. PPARα is the therapeutic target of the fibrates, which are widely used as hypolipidaemic compounds in the treatment of dyslipidaemia. PPARγ is a non-exclusive target of the thiazolidinediones, a new class of compounds with hypoglycaemic properties that are used to treat type II diabetes. Because of its involvement in lipid metabolism and skin homeostasis, it is likely that PPARβ/δ will become a therapeutic target in the near future.
4. Each PPAR isotype is associated with pathways that relate to carcinogenesis. Long-term activation of PPARα by peroxisome proliferators induces the development of hepatocarcinomas in rodent liver, but not in humans. PPARγ is thought to have overall anti-carcinogenic effects in many different cell types, due to its anti-proliferation, pro-differentiation and pro-apoptotic properties. PPARβ/δ is involved in the control of cell proliferation, cell differentiation and apoptosis, but its involvement in the development of tumours is unclear at present.
5. In the future, PPARγ, and perhaps PPARβ/δ, might become interesting therapeutic targets for the treatment of tumours. However, further investigation is needed at both the scientific and clinical levels.

要点翻译：

1. 过氧化物酶体增殖物激活受体（PPARs）属于核激素受体家族，是一类配体激活的转录因子。目前已鉴定出三种亚型：PPARα、PPARβ/δ和PPARγ。
2. PPARs可被内源性配体（脂肪酸及其衍生物）激活，作为这些配体的细胞内传感器，进而对脂质和葡萄糖代谢相关通路进行转录调控。
3. PPARα是贝特类药物的治疗靶点，这类广泛应用的降脂化合物用于治疗血脂异常。PPARγ是噻唑烷二酮类药物的非专属靶点，这类具有降糖特性的新型化合物用于治疗II型糖尿病。由于PPARβ/δ参与脂质代谢和皮肤稳态调控，该亚型很可能在近期成为新的治疗靶点。
4. 每种PPAR亚型均与致癌作用相关通路存在关联。过氧化物酶体增殖剂对PPARα的长期激活会诱导啮齿动物肝脏发生肝癌，但在人类中未见此效应。PPARγ因其具有抑制增殖、促进分化和促凋亡的特性，被认为在多种细胞类型中发挥总体抗癌作用。PPARβ/δ参与细胞增殖、分化和凋亡的调控，但其在肿瘤发生中的具体作用目前尚不明确。
5. 未来PPARγ（可能还包括PPARβ/δ）或将成为肿瘤治疗的重要靶点，但这仍需在科学研究和临床层面开展进一步探索。

英文摘要：

Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors that mediate the effects of fatty acids and their derivatives at the transcriptional level. Through these pathways, PPARs can regulate cell proliferation, differentiation and survival, so controlling carcinogenesis in various tissues. But what are the links between each PPAR isotype and carcinogenesis and what is the relevance of these findings to human pathology and therapy?

摘要翻译： 

过氧化物酶体增殖物激活受体（PPARs）是一类核激素受体，可在转录水平介导脂肪酸及其衍生物的效应。通过这些通路，PPARs能够调控细胞增殖、分化和存活，从而控制多种组织的癌变。然而，每一种PPAR亚型与癌变之间究竟存在怎样的联系？这些发现对人类病理及治疗又有何意义？

原文链接：

Peroxisome-proliferator-activated receptors and cancers: complex stories