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 g (PPARg) might be a target for pharmacological intervention in NB. We have previously demonstrated that the PPARg 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 kg1) 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 PPARg agonists may have a role in anti-tumoural strategies against NB.

In vivo effects of rosiglitazone in a human neuroblastoma xenograft / I.Cellai; G.Petrangolini; M.Tortoreto; G.Pratesi; P.Luciani; C.Deledda; S.Benvenuti; C.Ricordati; S.Gelmini; E.Ceni; A.Galli; M.Balzi; P.Faraoni; M.Serio; A.Peri. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - STAMPA. - 102:(2010), pp. 685-692.

In vivo effects of rosiglitazone in a human neuroblastoma xenograft

CELLAI, ILARIA;BENVENUTI, SUSANNA;GELMINI, STEFANIA;CENI, ELISABETTA;GALLI, ANDREA;BALZI, MANUELA;FARAONI, PAOLA;SERIO, MARIO;PERI, ALESSANDRO
2010

Abstract

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 g (PPARg) might be a target for pharmacological intervention in NB. We have previously demonstrated that the PPARg 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 kg1) 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 PPARg agonists may have a role in anti-tumoural strategies against NB.
2010
102
685
692
I.Cellai; G.Petrangolini; M.Tortoreto; G.Pratesi; P.Luciani; C.Deledda; S.Benvenuti; C.Ricordati; S.Gelmini; E.Ceni; A.Galli; M.Balzi; P.Faraoni; M.Serio; A.Peri
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/376193
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