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In vivo effects of rosiglitazone in a human neuroblastoma xenograft.

Cellai I, Petrangolini G, Tortoreto M, Pratesi G, Luciani P, Deledda C, Benvenuti S, Ricordati C, Gelmini S, Ceni E, Galli A, Balzi M, Faraoni P, Serio M, Peri A - Br. J. Cancer (2010)

Bottom Line: We have previously demonstrated that the PPARgamma 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.To our knowledge, this is the first demonstration that RGZ effectively inhibits tumour growth in a human NB xenograft and our results suggest that PPARgamma agonists may have a role in anti-tumoural strategies against NB.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Physiopathology, Center for Research, University of Florence, Italy.

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

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Related in: MedlinePlus

Immunohistochemistry (IHC) for CD-31 evaluation in tumour tissues from control (i.e., solvent treated) and rosiglitazone (RGZ)-treated (A, 2 weeks; B, 4 weeks) mice. Y axis: number of CD-31-positive cells per field. (C) Example of a field showing high CD-31 staining in the tissue sample from a control mouse. (D) Example of a field showing a few CD-31-positive cells after 4 weeks of treatment with RGZ ( × 100 magnification).
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fig6: Immunohistochemistry (IHC) for CD-31 evaluation in tumour tissues from control (i.e., solvent treated) and rosiglitazone (RGZ)-treated (A, 2 weeks; B, 4 weeks) mice. Y axis: number of CD-31-positive cells per field. (C) Example of a field showing high CD-31 staining in the tissue sample from a control mouse. (D) Example of a field showing a few CD-31-positive cells after 4 weeks of treatment with RGZ ( × 100 magnification).

Mentions: In the same tumour samples used for apoptosis assessment, tumour angiogenesis was investigated by determining the percentage of cells showing a positive staining for CD-31. The number of immunopositive cells seemed reduced (yet not significantly, P=0.058) after 2 weeks of RGZ treatment (Table 1 and Figure 6A). In tumours of mice treated with RGZ for 4 weeks, the reduction in CD-31-positive cells became statistically significant (P<0.005) (Table 1 and Figure 6B). A large variability among the different tumour samples of RGZ-treated mice was observed, and a strong inhibitory effect could be observed in some of them (Figures 6C–D).


In vivo effects of rosiglitazone in a human neuroblastoma xenograft.

Cellai I, Petrangolini G, Tortoreto M, Pratesi G, Luciani P, Deledda C, Benvenuti S, Ricordati C, Gelmini S, Ceni E, Galli A, Balzi M, Faraoni P, Serio M, Peri A - Br. J. Cancer (2010)

Immunohistochemistry (IHC) for CD-31 evaluation in tumour tissues from control (i.e., solvent treated) and rosiglitazone (RGZ)-treated (A, 2 weeks; B, 4 weeks) mice. Y axis: number of CD-31-positive cells per field. (C) Example of a field showing high CD-31 staining in the tissue sample from a control mouse. (D) Example of a field showing a few CD-31-positive cells after 4 weeks of treatment with RGZ ( × 100 magnification).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2837558&req=5

fig6: Immunohistochemistry (IHC) for CD-31 evaluation in tumour tissues from control (i.e., solvent treated) and rosiglitazone (RGZ)-treated (A, 2 weeks; B, 4 weeks) mice. Y axis: number of CD-31-positive cells per field. (C) Example of a field showing high CD-31 staining in the tissue sample from a control mouse. (D) Example of a field showing a few CD-31-positive cells after 4 weeks of treatment with RGZ ( × 100 magnification).
Mentions: In the same tumour samples used for apoptosis assessment, tumour angiogenesis was investigated by determining the percentage of cells showing a positive staining for CD-31. The number of immunopositive cells seemed reduced (yet not significantly, P=0.058) after 2 weeks of RGZ treatment (Table 1 and Figure 6A). In tumours of mice treated with RGZ for 4 weeks, the reduction in CD-31-positive cells became statistically significant (P<0.005) (Table 1 and Figure 6B). A large variability among the different tumour samples of RGZ-treated mice was observed, and a strong inhibitory effect could be observed in some of them (Figures 6C–D).

Bottom Line: We have previously demonstrated that the PPARgamma 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.To our knowledge, this is the first demonstration that RGZ effectively inhibits tumour growth in a human NB xenograft and our results suggest that PPARgamma agonists may have a role in anti-tumoural strategies against NB.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Physiopathology, Center for Research, University of Florence, Italy.

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

Show MeSH
Related in: MedlinePlus