RESUMEN
Drug delivery systems with targeting agents for precise drug release in cancer therapy are very significant and important. Herein, we report the rational design and synthesis of a DOX (doxorubicin) loaded UiO-68-type of nanoscale metal-organic framework (NMOF) with a tumor targeting agent (folic acid, FA), DOX@UiO-68-FA (3), as a multifunctional drug delivery system for hepatoma (Hep G2) therapy via tail-vein injection. Compared to free DOX, FA-unloaded DOX@Mi-UiO-68 (2), 3 exhibits a much higher antitumor efficacy, which was confirmed by cell imaging, standard 3-(4,5-dimethylthiahiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) proliferation and in vivo experiments.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Doxorrubicina/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/química , Compuestos Organometálicos/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/patología , Ratones , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Relación Estructura-ActividadRESUMEN
AIM: To study the influence of CXCR4/stromal cell-derived factor-1 (SDF-1) axis on E-cadherin/ß-catenin complex expression in HT29 colon cancer cells and its underlying mechanisms. METHODS: Effect of SDF-1 on E-cadherin/ß-catenin expression was detected by immunocytochemistry. E-cadherin and ß-catenin mRNA expression levels were measured by reverse transcriptase-polymerase chain reaction. SDF-1-induced phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT and ß-catenin was detected by Western blotting. RESULTS: The E-cadherin and ß-catenin mRNA expression levels in HT29 cells were lower 48 h after incubated with SDF-1 at the concentrations of 20 and 40 ng/mL (P<0.05). SDF-1-induced significant phosphorylation of PI3K/AKT and ß-catenin. AMD3100 and LY294002 inhibited the phosphorylation of PI3K/AKT and ß-catenin. CONCLUSION: SDF-1 down-regulates the E-cadherin/ß-catenin complex expression in HT29 cells by decreasing mRNA synthesis and increasing ß-catenin phosphorylation.