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Genet Mol Res ; 13(3): 5094-106, 2014 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-25061734

RESUMO

This study aimed to investigate the inhibition of vascular endothelial growth factor (VEGF) by small hairpin RNA (shRNA) interference combined with radiotherapy on the growth of cervical cancer SiHa cell xenografts in nude mice. The effective pVEGF-shRNA plasmid was screened by reverse transcription-polymerase chain reaction (RT-PCR), and the cell apoptosis rate was estimated by flow cytometry. A nude mouse cervical xenograft model was established and all models were divided into four groups: blank control, VEGF shRNA, radiotherapy, and combined treatment. We calculated the tumor growth curve and the inhibitory rate. The histopathological changes of the microvascular density and VEGF protein expression were observed by immunohistochemistry. The expressions of VEGF and hypoxia inducible factor-1α (HIF-1α) proteins in the tumor tissue were analyzed via Western blot. VEGF shRNA interference inhibited the expression of radiation-induced VEGF (P < 0.05), induced apoptosis (P < 0.05), downregulated the HIF-1α protein, and reduced angiogenesis. Compared with the other three groups, the combined treatment group showed the most significant effects (P < 0.01). VEGF shRNA interference combined with radiotherapy promotes the radiosensitivity of tumors via improvement of the hypoxic microenvironment.


Assuntos
RNA Interferente Pequeno/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/terapia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Apoptose , Terapia Combinada , Progressão da Doença , Feminino , Raios gama , Expressão Gênica , Terapia Genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neovascularização Patológica , RNA Interferente Pequeno/metabolismo , Transplante Heterólogo , Carga Tumoral , Neoplasias do Colo do Útero/irrigação sanguínea , Neoplasias do Colo do Útero/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
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