In vitro and in vivo radiosensitization induced by hydroxyapatite nanoparticles.
Neuro Oncol
; 15(7): 880-90, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23519742
ABSTRACT
BACKGROUND:
Previous study showed that hydroxyapatite nanoparticles (nano-HAPs) inhibited glioma growth in vitro and in vivo; and in a drug combination, they could reduce adverse reactions. We investigated the possible enhancement of radiosensitivity induced by nano-HAPs.METHODS:
In vitro radiosensitization of nano-HAPs was measured using a clonogenic survival assay in human glioblastoma U251 and breast tumor brain metastatic tumor MDA-MB-231BR cells. DNA damage and repair were measured using γH2AX foci, and mitotic catastrophe was determined by immunostaining. The effect of nano-HAPs on in vivo tumor radiosensitivity was investigated in a subcutaneous and an orthotopic model.RESULTS:
Nano-HAPs enhanced each cell line's radiosensitivity when the exposure was 1 h before irradiation, and they had no significant effect on irradiation-induced apoptosis or on the activation of the G2 cell cycle checkpoint. The number of γH2AX foci per cell was significantly large at 24 h after the combination modality of nano-HAPs + irradiation compared with single treatments. Mitotic catastrophe was also significantly increased at an interval of 72 h in tumor cells receiving the combined modality compared with the individual treatments. In a subcutaneous model, nano-HAPs caused a larger than additive increase in tumor growth delay. In an orthotopic model, nano-HAPs significantly reduced tumor growth and extended the prolongation of survival induced by irradiation.CONCLUSIONS:
These results show that nano-HAPs can enhance the radiosensitivity of tumor cells in vitro and in vivo through the inhibition of DNA repair, resulting in an increase in mitotic catastrophe.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
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Tolerância a Radiação
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Neoplasias Encefálicas
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Neoplasias da Mama
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Durapatita
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Glioblastoma
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Nanopartículas
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Neuro Oncol
Assunto da revista:
NEOPLASIAS
/
NEUROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China