Cellai I, Benvenuti S, Luciani P, Galli A, Ceni E, Simi L, Baglioni S, Muratori M, Ottanelli B, Serio M, Thiele C J, Peri A
Endocrine Unit, Department of Clinical Physiopathology, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders (DENOThe), University of Florence, Florence, Italy.
Br J Cancer. 2006 Oct 9;95(7):879-88. doi: 10.1038/sj.bjc.6603344. Epub 2006 Sep 12.
Neuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARgamma. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 microM RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARgamma as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARgamma responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARgamma activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARgamma transactivation. This finding indicates that PPARgamma activity may be useful to select those patients, for whom PPARgamma agonists may have a beneficial therapeutic effect.
神经母细胞瘤（NB）是婴儿中最常见的颅外实体瘤。不幸的是，大多数儿童就诊时已处于疾病晚期，预后较差。在本研究中，我们评估了过氧化物酶体增殖物激活受体γ（PPARγ）激动剂罗格列酮（RGZ）在两种表达PPARγ的NB细胞系（SK-N-AS和SH-SY5Y）中的作用。罗格列酮对SK-N-AS细胞增殖和活力的抑制作用比对SH-SY5Y细胞更强。此外，20微摩尔的RGZ显著抑制了SK-N-AS细胞的黏附、侵袭能力并诱导其凋亡，但对SH-SY5Y细胞无此作用。由于SK-N-AS和SH-SY5Y细胞对RGZ的反应不同，因此对PPARγ作为转录激活因子的功能进行了评估。值得注意的是，使用PPARγ反应元件进行的瞬时转录实验表明，RGZ使SK-N-AS细胞中的报告基因活性增加了三倍，而在SH-SY5Y细胞中未观察到这种效应。不同的PPARγ活性可能是由于在SK-N-AS细胞中观察到的磷酸化（即无活性）蛋白的量明显较低。据我们所知，这是首次证明NB细胞对RGZ的不同反应可能与PPARγ反式激活的差异有关。这一发现表明，PPARγ活性可能有助于筛选出那些可能从PPARγ激动剂治疗中获益的患者。
