Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
J Hepatocell Carcinoma. 2014 Aug 26;1:127-35. doi: 10.2147/JHC.S48512. eCollection 2014.
Hepatocellular carcinoma (HCC) is the major leading cause of cancer death worldwide. Hepatitis B virus, hepatitis C virus, alcohol consumption, non-alcoholic fatty liver disease, and diabetes are the major risks for developing HCC. Until now, recurrence and metastasis are the major cause of death in HCC patients. Therefore, identification of new effective molecular targets is an urgent need for treatment of HCC. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor which could be activated by PPARγ agonists such as thiazolidinediones, and natural PPARγ ligand (such as 15-deoxy-Δ12,14-prostaglandin J2, 15d-PGJ2). Increasing in vitro and in vivo evidence has demonstrated that PPARγ agonists exhibit an inhibitory role on tumor cell growth, migration, and invasion, suggesting that PPARγ activation may play an important role in the regulation of growth of HCC. It has been reported that PPARγ activation by thiazolidinediones or overexpression of PPARγ by virus-mediated gene transfer has shown growth inhibitory effects in hepatoma cells, but the expression level of PPARγ in HCC tissues still remains conflicting. Notably, a novel PPARγ agonist, honokiol, has recently been found to activate the PPARγ/RXR heterodimer, and has also exhibited significant anti-cancer effects in hepatoma cells. In the present review, we summarized studies on the role and the molecular regulation of PPARγ in HCC development in vitro and in vivo. PPARγ has the potential to be a therapeutic target for future treatment of HCC.
肝细胞癌（HCC）是全球癌症死亡的主要原因。乙型肝炎病毒、丙型肝炎病毒、饮酒、非酒精性脂肪性肝病和糖尿病是导致 HCC 的主要危险因素。到目前为止，复发和转移是 HCC 患者死亡的主要原因。因此，寻找新的有效分子靶点是 HCC 治疗的迫切需要。过氧化物酶体增殖物激活受体 γ（PPARγ）是一种配体激活的核受体，可被 PPARγ 激动剂（如噻唑烷二酮类和天然 PPARγ 配体（如 15-脱氧-Δ12,14-前列腺素 J2、15d-PGJ2）激活。越来越多的体外和体内证据表明，PPARγ 激动剂对肿瘤细胞的生长、迁移和侵袭具有抑制作用，这表明 PPARγ 激活可能在 HCC 的生长调节中发挥重要作用。据报道，噻唑烷二酮类药物激活 PPARγ 或病毒介导的基因转移过表达 PPARγ 可抑制肝癌细胞的生长，但 HCC 组织中 PPARγ 的表达水平仍存在争议。值得注意的是，最近发现一种新型 PPARγ 激动剂 honokiol 可激活 PPARγ/RXR 异二聚体，并在肝癌细胞中显示出显著的抗癌作用。在本综述中，我们总结了 PPARγ 在 HCC 体内外发展中的作用和分子调控的研究。PPARγ 有可能成为未来 HCC 治疗的一个治疗靶点。
