Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

Zhanrong Li,1,* Xianghua Wu,1,* Jingguo Li,2 Lin Yao,1 Limei Sun,1 Yingying Shi,1 Wenxin Zhang,1 Jianxian Lin,1 Dan Liang,1 Yongping Li1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People&a...

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Autores principales:	Li ZR, Wu XH, Li JG, Yao L, Sun LM, Shi YY, Zhang WX, Lin JX, Liang D, Li YP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3ca999e208bf416d8371884bfd5aa584
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spelling	oai:doaj.org-article:3ca999e208bf416d8371884bfd5aa5842021-12-02T05:02:05ZAntitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model1176-91141178-2013https://doaj.org/article/3ca999e208bf416d8371884bfd5aa5842012-05-01T00:00:00Zhttp://www.dovepress.com/antitumor-activity-of-celastrol-nanoparticles-in-a-xenograft-retinobla-a9866https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Zhanrong Li,1,* Xianghua Wu,1,* Jingguo Li,2 Lin Yao,1 Limei Sun,1 Yingying Shi,1 Wenxin Zhang,1 Jianxian Lin,1 Dan Liang,1 Yongping Li1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People&#39;s Republic of China*These authors contributed equally to this workBackground: Celastrol, a Chinese herbal medicine, has shown antitumor activity against various tumor cell lines. However, the effect of celastrol on retinoblastoma has not yet been analyzed. Additionally, the poor water solubility of celastrol restricts further therapeutic applications. The goal of this study was to evaluate the effect of celastrol nanoparticles (CNPs) on retinoblastoma and to investigate the potential mechanisms involved.Methods: Celastrol-loaded poly(ethylene glycol)-block-poly(&epsilon;-caprolactone) nanopolymeric micelles were developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulf-ophenyl)-2H tetrazolium monosodium salt (WST-8) assay was used to determine the inhibitory effect of CNPs on SO-Rb 50 cell proliferation in vitro. Immunofluorescence was used to evaluate the apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-&kappa;B p65, and phospo-NF-&kappa;B p65 proteins was assessed by Western blotting. A human retinoblastoma xenograft model was used to evaluate the inhibitory effects of CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used to assess the apoptotic effects of CNPs on retinoblastoma.Results: CNPs inhibit the proliferation of SO-Rb 50 cells in a dose- and time-dependent manner with an IC50 of 17.733 &micro;g/mL (celastrol-loading content: 7.36%) after exposure to CNPs for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner. The expression of Bcl-2, NF-&kappa;B p65, and phospo-NF-&kappa;B p65 proteins decreased after exposure to CNPs 54.4 &micro;g/mL for 48 hours. Additionally, the Bax/Bcl-2 ratio increased, whereas the expression of Bax itself was not significantly altered. CNPs inhibit the growth of retinoblastoma and induce apoptosis in retinoblastoma cells in mice.Conclusion: CNPs inhibit the growth of retinoblastoma in mouse xenograft model by inducing apoptosis in SO-Rb 50 cells, which may be related to the increased Bax/Bcl-2 ratio and the inhibition of NF-&kappa;B. CNPs may represent a potential alternative treatment for retinoblastoma.Keywords: apoptosis, SO-Rb 50 cells, poly(ethylene glycol)-block-poly(&epsilon;-caprolactone), nanopolymeric micelles, celastrol nanoparticles&nbsp;Li ZRWu XHLi JGYao LSun LMShi YYZhang WXLin JXLiang DLi YPDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2389-2398 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li ZR Wu XH Li JG Yao L Sun LM Shi YY Zhang WX Lin JX Liang D Li YP Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model
description	Zhanrong Li,1,* Xianghua Wu,1,* Jingguo Li,2 Lin Yao,1 Limei Sun,1 Yingying Shi,1 Wenxin Zhang,1 Jianxian Lin,1 Dan Liang,1 Yongping Li1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People&#39;s Republic of China*These authors contributed equally to this workBackground: Celastrol, a Chinese herbal medicine, has shown antitumor activity against various tumor cell lines. However, the effect of celastrol on retinoblastoma has not yet been analyzed. Additionally, the poor water solubility of celastrol restricts further therapeutic applications. The goal of this study was to evaluate the effect of celastrol nanoparticles (CNPs) on retinoblastoma and to investigate the potential mechanisms involved.Methods: Celastrol-loaded poly(ethylene glycol)-block-poly(&epsilon;-caprolactone) nanopolymeric micelles were developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulf-ophenyl)-2H tetrazolium monosodium salt (WST-8) assay was used to determine the inhibitory effect of CNPs on SO-Rb 50 cell proliferation in vitro. Immunofluorescence was used to evaluate the apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-&kappa;B p65, and phospo-NF-&kappa;B p65 proteins was assessed by Western blotting. A human retinoblastoma xenograft model was used to evaluate the inhibitory effects of CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used to assess the apoptotic effects of CNPs on retinoblastoma.Results: CNPs inhibit the proliferation of SO-Rb 50 cells in a dose- and time-dependent manner with an IC50 of 17.733 &micro;g/mL (celastrol-loading content: 7.36%) after exposure to CNPs for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner. The expression of Bcl-2, NF-&kappa;B p65, and phospo-NF-&kappa;B p65 proteins decreased after exposure to CNPs 54.4 &micro;g/mL for 48 hours. Additionally, the Bax/Bcl-2 ratio increased, whereas the expression of Bax itself was not significantly altered. CNPs inhibit the growth of retinoblastoma and induce apoptosis in retinoblastoma cells in mice.Conclusion: CNPs inhibit the growth of retinoblastoma in mouse xenograft model by inducing apoptosis in SO-Rb 50 cells, which may be related to the increased Bax/Bcl-2 ratio and the inhibition of NF-&kappa;B. CNPs may represent a potential alternative treatment for retinoblastoma.Keywords: apoptosis, SO-Rb 50 cells, poly(ethylene glycol)-block-poly(&epsilon;-caprolactone), nanopolymeric micelles, celastrol nanoparticles&nbsp;
format	article
author	Li ZR Wu XH Li JG Yao L Sun LM Shi YY Zhang WX Lin JX Liang D Li YP
author_facet	Li ZR Wu XH Li JG Yao L Sun LM Shi YY Zhang WX Lin JX Liang D Li YP
author_sort	Li ZR
title	Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model
title_short	Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model
title_full	Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model
title_fullStr	Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model
title_full_unstemmed	Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model
title_sort	antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/3ca999e208bf416d8371884bfd5aa584
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_version_	1718400761875922944

Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

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