In vivo effects of rosiglitazone in a human neuroblastoma xenograft

被引:26
作者
Cellai, I. [1 ]
Petrangolini, G. [2 ]
Tortoreto, M. [2 ]
Pratesi, G. [2 ]
Luciani, P. [1 ]
Deledda, C. [1 ]
Benvenuti, S. [1 ]
Ricordati, C. [3 ]
Gelmini, S. [4 ]
Ceni, E. [5 ]
Galli, A. [5 ]
Balzi, M. [6 ]
Faraoni, P. [6 ]
Serio, M. [1 ]
Peri, A. [1 ]
机构
[1] Univ Florence, Ctr Res Transfer & High Educ Chron Inflammatory D, Dept Clin Physiopathol, Endocrine Unit, I-50139 Florence, Italy
[2] Ist Nazl Tumori, Fdn IRCCS, Dept Expt Oncol & Labs, I-20133 Milan, Italy
[3] Univ Milan, Sch Vet Med, Sect Vet & Avian Pathol, Dept Vet Pathol Hyg & Publ Hlth, I-20133 Milan, Italy
[4] Univ Florence, Ctr Res Transfer & High Educ Chron Inflammatory D, Dept Clin Physiopathol, Clin Biochem Unit, I-50139 Florence, Italy
[5] Univ Florence, Ctr Res Transfer & High Educ Chron Inflammatory D, Dept Clin Physiopathol, Gastroenterol Unit, I-50139 Florence, Italy
[6] Univ Florence, Ctr Res Transfer & High Educ Chron Inflammatory D, Dept Clin Physiopathol, Radiat Biol Unit, I-50139 Florence, Italy
关键词
PPAR gamma; RGZ; NB; xenograft; ACTIVATED-RECEPTOR-GAMMA; HIGH-RISK NEUROBLASTOMA; HUMAN PROSTATE-CANCER; PPAR-GAMMA; CELL-LINES; LUNG-CANCER; PHASE-II; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); LIGAND TROGLITAZONE; GROWTH-INHIBITION;
D O I
10.1038/sj.bjc.6605506
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Neuroblastoma (NB) is the most common extra-cranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. There is in vitro evidence that the peroxisome proliferator-activated receptor gamma (PPAR gamma) might be a target for pharmacological intervention in NB. We have previously demonstrated that the PPAR gamma agonist rosiglitazone (RGZ) exerts strong anti-tumoural effects in the human NB cell line, SK-N-AS. The aim of this study was to evaluate whether RGZ maintains its anti-tumoural effects against SK-N-AS NB cells in vivo. METHODS AND RESULTS: For this purpose, tumour cells were subcutaneously implanted in nude mice, and RGZ (150 mg kg(-1)) was administered by gavage daily for 4 weeks. At the end of treatment, a significant tumour weight inhibition (70%) was observed in RGZ-treated mice compared with control mice. The inhibition of tumour growth was supported by a strong anti-angiogenic activity, as assessed by CD-31 immunostaining in tumour samples. The number of apoptotic cells, as determined by cleaved caspase-3 immunostaining, seemed lower in RGZ-treated animals at the end of the treatment period than in control mice, likely because of the large tumour size observed in the latter group. CONCLUSIONS: To our knowledge, this is the first demonstration that RGZ effectively inhibits tumour growth in a human NB xenograft and our results suggest that PPAR gamma agonists may have a role in anti-tumoural strategies against NB. British Journal of Cancer (2010) 102, 685-692. doi:10.1038/sj.bjc.6605506 www.bjcancer.com Published online 12 January 2010 (C) 2010 Cancer Research UK
引用
收藏
页码:685 / 692
页数:8
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