Synergic effects of the combination of VEGF-targeted shRNA and taxol on human prostate cancer DU145 both in vitro and in vivo / 药学学报
Acta Pharmaceutica Sinica
; (12): 296-302, 2009.
Article
em Zh
| WPRIM
| ID: wpr-278267
Biblioteca responsável:
WPRO
ABSTRACT
In this study, the antitumor activities of VEGF shRNA and tubulin inhibitors on human prostate cancer DU145 cells was investigated, and shRNA transient expression plasmid pCSH1-VEGF targeting VEGF mRNA was constructed. The silence efficiency of pCSH1-VEGF was detected by RT-PCR assay, Western blotting, and Matrigel invasion assay. The sensitivity change of DU145 cells to Taxol and vincristine (VCR) was measured by MTT assay. To detect the effects of pCSH1-VEGF and Taxol in vivo, nude mice model of DU145 xenograft tumor was established by subcutaneous inoculation. The results showed that transcription and expression of VEGF were knocked by pCSH1-VEGF in DU145 cells. Matrigel invasion assay results showed that pCSH1-VEGF significantly reduced the migration of DU145 cells with inhibitory rate of 56.1%. Furthermore, pCSH1-VEGF enhanced the sensitivity of DU145 cells to Taxol and vincristine, and the values of IC50 decreased by 77.3% and 92.6%, respectively. In vivo experiment showed that Taxol, pCSH1-VEGF, combination of pCSH1-VEGF and Taxol inhibited tumor growth by the rates of 48.8%, 56.2% and 81.8%, respectively. The coefficient of drug interaction (CDI) of pCSH1-VEGF and Taxol was 0.82. The data suggested that VEGF shRNA could significantly enhance the sensitivity of human prostate cancer to tubulin inhibitors.
Texto completo:
1
Índice:
WPRIM
Assunto principal:
Patologia
/
Farmacologia
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Plasmídeos
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Neoplasias da Próstata
/
Vincristina
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Transfecção
/
Movimento Celular
/
Paclitaxel
/
RNA Interferente Pequeno
/
Interferência de RNA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
/
Male
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Ano de publicação:
2009
Tipo de documento:
Article