Peroxisome Proliferator-Activated Receptor γ Pathway Targeting in Carcinogenesis: Implications for Chemoprevention
Peroxisome Proliferator-Activated Receptor γ Pathway Targeting in Carcinogenesis: Implications for Chemoprevention
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DOI：
10.1158/1078-0432.ccr-08-0326
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发表时间：
2009-01-01
影响因子：
11.5
通讯作者：
Ondrey, Frank
中科院分区：
文献类型：
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作者：
Ondrey, Frank
过氧化物酶体增殖体激活受体(PPAR) γ是核受体超家族的成员之一，该家族包含超过80个已知的受体。PFAR γ激活剂是一组多种多样的药物，从内源性脂肪酸或衍生物(亚麻酸、亚油酸和15-deoxy-Delta（12,14)-前列腺素J(2)）到美国食品和药物管理局批准的用于治疗糖尿病的噻唑烷二酮类药物[吡格列酮（Actos）和罗格列酮（文迪雅）]。一旦被激活，PFAR γ将优先与类视黄酸X受体α结合，并在几种组织类型中发出抗增殖、抗血管生成和前分化信号，从而使其成为下调癌变的非常有用的靶点。尽管ppar - γ激活剂对细胞系显示出许多抗癌作用，但它们在人类晚期癌症临床试验中的进展却取得了有限的成功。本文将回顾PPAR γ激活和靶向在癌症预防中的转化发现，因为它们与PFAR γ激活剂在临床上作为癌症化学预防策略的潜在应用有关。
The peroxisome proliferator-activated receptor (PPAR) gamma is one member of the nuclear receptor superfamily that contains in excess of 80 described receptors. PFAR gamma activators are a diverse group of agents that range from endogenous fatty acids or derivatives (linolenic, linoleic, and 15-deoxy-Delta(12,14)-prostaglandin J(2)) to Food and Drug Administration-approved thiazolidinedione drugs [pioglitazone (Actos) and rosiglitazone (Avandia)] for the treatment of diabetes. Once activated, PFAR gamma will preferentially bind with retinoid X receptor alpha and signal antiproliferative, antiangiogenic, and prodifferentiation pathways in several tissue types, thus making it a highly useful target for down-regulation of carcinogenesis. Although PPAR-gamma activators show many anticancer effects on cell lines, their advancement into human advanced cancer clinical trials has met with limited success. This article will review translational findings in PPAR gamma activation and targeting in carcinogenesis prevention as they relate to the potential use of PFAR gamma activators clinically as cancer chemoprevention strategies.