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Future Oncol ; 10(14): 2161-75, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25471031

RESUMO

AIMS: The intention of this work was to lift saponin supported tumor targeted therapies onto the next level by using targeted toxins in nude mice xenotransplant models. MATERIALS & METHODS: Combined application of dianthin coupled to EGF and saponin SO-1861 was tested in a xenograft model of colon carcinoma. In vitro cytotoxicity was tested in real-time in NIH3T3 cells (no human EGF receptor expression), HER14 and human colon carcinoma HCT116 (both EGF receptor overexpressing) cells. A xenograft model was established using HCT116 cells and tumor-bearing animals were treated with SO-1861 (30 µg/treatment) and dianthin coupled to EGF (0.35 µg/treatment). Tumor progression was monitored, using (18)F-2-fluor-2-desoxy-d-glucose, by small animal PET and by x-ray computed tomography. RESULTS: In vitro results demonstrated a high-receptor specificity and the in vivo experiment showed a progressive reduction of the tumor volume and glycolytic activity in the treated group (>95% reduction; p < 0.05). CONCLUSION: This therapy has great advantage because of high specificity, low side effects and great effectiveness for future development in the treatment of colon cancer.


Assuntos
Carcinoma/patologia , Neoplasias do Colo/patologia , Imunotoxinas/farmacologia , Saponinas/farmacologia , Animais , Carcinoma/diagnóstico , Carcinoma/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/tratamento farmacológico , Dianthus/química , Modelos Animais de Doenças , Quimioterapia Combinada , Fator de Crescimento Epidérmico , Hemólise/efeitos dos fármacos , Humanos , Imunotoxinas/administração & dosagem , Imunotoxinas/efeitos adversos , Masculino , Camundongos , Tomografia por Emissão de Pósitrons , Proteínas Inativadoras de Ribossomos Tipo 1 , Saponinas/administração & dosagem , Saponinas/efeitos adversos , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
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