In vivo effects of rosiglitazone in a human neuroblastoma xenograft

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 kg À1 ) 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.

PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs

“…The distinct response of the two NB cell lines is likely due to a reduced phosphorylation of PPAR- γ and consequently its increased activity in SK-N-AS cells. Cellai and colleagues also evaluated the in vivo effect of TZDs in NB xenograft models, confirming their previous in vitro observations [ 24 ]. Indeed rosiglitazone (150 mg/kg/day) for 4 weeks significantly reduced tumor growth (−70%) as compared to control mice [ 24 ].…”

PPARs and Mitochondrial Metabolism: From NAFLD to HCC

“…As the master regulator of adipogenic differentiation, PPAR γ has been described to promote differentiation programs in a variety of tumor cell types [143, 144], inducing cell-cycle arrest [145], apoptosis/anoikis [146–148], and inhibiting EMT [149, 150], angiogenesis [151], and metastasis [152]. …”

PPARγ agonists promote differentiation of cancer stem cells by restraining YAP transcriptional activity

“…Mice were administered Rosiglitazone (100mg/kg) orally five times a week for four weeks upon cell implantation and tumor volume was measured bi weekly for 4 weeks. The dosage was selected in line with previously published studies [ 32 , 33 ]. Figure 4A shows that Rosi treatment significantly delayed tumor growth as evidenced by reduced tumor volumes over the same time period.…”