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SHR Neuro Cancer Cardio Lipid Metab Microb

Hoffmann, K; Franz, C; Xiao, Z; Mohr, E; Serba, S; Büchler, MW; Schemmer, P.
Sorafenib modulates the gene expression of multi-drug resistance mediating ATP-binding cassette proteins in experimental hepatocellular carcinoma.
Anticancer Res. 2010; 30(11):4503-4508
Web of Science PubMed

 

Leading authors Med Uni Graz
Schemmer Peter
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Abstract:
High ATP-binding cassette (ABC) protein expression leads to intrinsic drug resistance of hepatocellular carcinoma (HCC). The aim of this study was to investigate the potential chemosensitizing effects of sorafenib on the multi-drug resistance (MDR) phenotype. The ABC-protein gene expression and the cellular survival were determined by RT-PCR analysis and MTT assay in HUH7 cells. Sorafenib inhibits MDR. The ABC-protein mRNA expression decreased by up to 51% (p ≤ 0.01). Addition of sorafenib to conventional chemotherapy restored the chemosensitivity. Combination of gemcitabine plus sorafenib decreased the ABC-protein mRNA levels by up to 77%, compared to gemcitabine monotherapy (p ≤ 0.001). Doxorubicin plus sorafenib decreased the ABC-protein mRNA levels up to 74% compared to doxorubicin monotherapy (p ≤ 0.001). This study provides evidence that the MDR phenotype of HCC cells can be modulated by the multi-kinase inhibitor sorafenib and consequentially may lead towards personalized therapies in patients with highly resistant tumors.
Find related publications in this database (using NLM MeSH Indexing)
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Benzenesulfonates - administration & dosage
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Cell Proliferation - drug effects
Deoxycytidine - administration & dosage
Deoxycytidine - analogs & derivatives
Doxorubicin - administration & dosage
Drug Resistance, Multiple - drug effects
Drug Resistance, Neoplasm - drug effects
Gene Expression Regulation, Neoplastic - drug effects
Humans -
Liver Neoplasms - drug therapy
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Multidrug Resistance-Associated Proteins - genetics
Multidrug Resistance-Associated Proteins - metabolism
Niacinamide - analogs & derivatives
Phenylurea Compounds -
Pyridines - administration & dosage
RNA, Messenger - genetics
Reverse Transcriptase Polymerase Chain Reaction -
Survival Rate -
Tumor Cells, Cultured -

Find related publications in this database (Keywords)
Tyrosine kinase pathway
P-glycoprotein
chemosensitivity sorafenib
multidrug resistance
hepatocellular carcinoma cells
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