过氧化物酶体增殖物激活受体α、γ激动剂与肿瘤

Peroxisome proliferator-activated receptors α,γ agonists and tumors

过氧化物酶体增殖物激活受体(PPAR)属于核激素受体超家族,现已知有3种亚型:PPARα、PPARβ/δ和PPARγ,其中PPARα和PPARγ分别是高血脂和糖尿病治疗药物的靶点,以PPARβ/δ为靶点的药物也已进入临床试验阶段。然而,近年来一些临床前及临床试验结果提示,PPARα/γ和PPARβ/δ激动剂可诱发小鼠多种肿瘤,PPARγ激动剂吡格列酮可能与人类膀胱癌发生有关。因此,PPAR与肿瘤的关系引起人们关注。本文综述了PPARα和PPARγ激动剂与肿瘤的关系,以期为PPAR激动剂的安全使用及进一步研发提供参考。

Peroxisome proliferator-activated receptors（PPAR）are members of the nuclear hormone receptor superfamily. So far,three PPAR isotypes（PPARα,PPARβ/δ and PPARγ） have been identified,PPARα and PPARγ agonists have been used in clinic for treatment of hyperlipidemia and diabetes mellitus,respectively. Meanwhile,candidates targeting PPARβ/δ have entered the clinical study. However,some pre-clinical and clinical studies have indicated that some agonists of PPARα/γ and PPARβ/δ can induce various tumors in mice,and PPARγ agonist pioglitazone may enhance the bladder cancer risk in humans. Therefore,the role of PPAR agonists in tumorigenesis has aroused much attention. This review mainly focuses on the progress in PPARα and PPARγagonists in tumors,aiming to provide more information for the safe medication and further development of PPAR agonists.