Increase of doxorubicin sensitivity by doxorubicin-loading into nanoparticles for hepatocellular carcinoma cells in vitro and in vivo

Hepatocellular carcinoma (HCC) is known to be chemoresistant to anticancer drugs due to the multidrug resistant (MDR) transporters expression. Here, we compared in vitro and in vivo the anti-tumor efficacy of doxorubicin-loaded polyisohexylcyanoacrylate nanoparticles (PIHCA-Dox) versus free doxorubi...

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Bibliographic Details
Published in:Journal of hepatology 2005-05, Vol.42 (5), p.736-743
Main Authors: Barraud, Luc, Merle, Philippe, Soma, Emilienne, Lefrançois, Lydie, Guerret, Sylviane, Chevallier, Michèle, Dubernet, Catherine, Couvreur, Patrick, Trépo, Christian, Vitvitski, Ludmila
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - pharmacology
Biological and medical sciences
Carcinoma, Hepatocellular - drug therapy
Cell Line, Tumor
Chemotherapy
Cyanoacrylates
Disease Models, Animal
Doxorubicin - pharmacology
Drug Resistance, Neoplasm
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Regulation, Neoplastic
Genes, myc - genetics
Hepatocellular carcinoma
Humans
In Vitro Techniques
Liver Neoplasms, Experimental - drug therapy
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Membrane Transport Proteins - genetics
Mice
Mice, Transgenic
Multidrug resistance
Multidrug Resistance-Associated Proteins - genetics
Nanoparticles
Transgenic mice
Tumors
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Summary:Hepatocellular carcinoma (HCC) is known to be chemoresistant to anticancer drugs due to the multidrug resistant (MDR) transporters expression. Here, we compared in vitro and in vivo the anti-tumor efficacy of doxorubicin-loaded polyisohexylcyanoacrylate nanoparticles (PIHCA-Dox) versus free doxorubicin (Dox). These nanoparticles are known to overcome the MDR phenotype. We first determined in vitro the 50% inhibition concentration (IC 50) of these drugs on different human hepatoma cell lines. Secondly, the efficacy of the drugs in vivo was determined on the X/ myc transgenic murine model of HCC by histological counting of apoptotic tumorous hepatocytes and by TUNEL labeling. We characterized by semi-quantitative RT-PCR the MDR-related gene ( mdr1, mdr3, mrp1) expression pattern in this model. In vitro, IC 50 was reduced with PIHCA-Dox versus Dox for Huh7 (1.7-fold reduction; P
ISSN:0168-8278
1600-0641
DOI:10.1016/j.jhep.2004.12.035