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J Exp Clin Cancer Res ; 29: 13, 2010 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-20158915

RESUMO

BACKGROUND: Genome-wide RNA interference screening study revealed that loss of expression of insulin-like growth factor binding protein 7 (IGFBP7) is a critical step in development of a malignant melanoma (MM), and this secreted protein plays a central role in apoptosis of MM. In this study we constructed pcDNA3.1-IGFBP7 to obtain high expression of IGBPF7 and to inhibit the growth of MM in C57BL/6J mice. METHODS: pcDNA3.1-IGFBP7 was transfected into B16-F10 cell, the expression of IGFBP7 was detected by RT-PCR and western blot. The proliferations and apoptosis rates of transfected and control cells were measured by CCK8 and FCM, respectively. The tumorigenicity and tumor growth in both pcDNA3.1-IGFBP7 group and control groups were studied in C57BL/6J mice model. IGFBP7, caspase-3, and VEGF expressions in tumor tissue were measured by immunohistochemistry. Apoptosis of tumors were detected by TUNEL. RESULTS: We demonstrated this plasmid inhibited proliferation of B16-F10 melanoma cells efficiently in vivo, exploiting the high expression of IGFBP7. More importantly, in-vivo transfection of pcDNA3.1-IGFBP7 inhibited MM growth in C57BL/6J mice. The inhibition of MM growth was proved owing to apoptosis and reduced expression of VEGF induced by pcDNA3.1-IGFBP7. CONCLUSIONS: These results suggest a potential new clinical strategy for MM gene treatment.


Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Melanoma Experimental/terapia , Neoplasias Cutâneas/terapia , Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose , Sobrevivência Celular , DNA Complementar , Terapia Genética , Camundongos , Plasmídeos , Transfecção
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