Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin

Autor: Byung Mu Lee, Hae Young Chung, Yu Jin Shin, A Jin Won, Jee H. Jung, Tae Hyung Kim, Wahn Soo Choi, Hyung Sik Kim
Rok vydání: 2013
Předmět:
ATP Binding Cassette Transporter
Subfamily B
Blotting
Western
Biophysics
Apoptosis
Breast Neoplasms
Pharmacology
Resveratrol
Real-Time Polymerase Chain Reaction
Biochemistry
chemistry.chemical_compound
Mice
Breast cancer
Nude mouse
In vivo
Antineoplastic Combined Chemotherapy Protocols
Stilbenes
polycyclic compounds
medicine
Tumor Cells
Cultured
Animals
Humans
Doxorubicin
Tissue Distribution
ATP Binding Cassette Transporter
Subfamily B
Member 1
RNA
Messenger
skin and connective tissue diseases
Cytotoxicity
Molecular Biology
P-glycoprotein
Cell Proliferation
Mice
Inbred BALB C
biology
Reverse Transcriptase Polymerase Chain Reaction
organic chemicals
technology
industry
and agriculture
Drug Synergism
medicine.disease
biology.organism_classification
Drug Resistance
Multiple
carbohydrates (lipids)
chemistry
Drug Resistance
Neoplasm
Cancer cell
biology.protein
Female
Multidrug Resistance-Associated Proteins
medicine.drug
Zdroj: Biochimica et biophysica acta. 1840(1)
ISSN: 0006-3002
Popis: Background Multidrug resistance is a major problem in the treatment of breast cancer, and a number of studies have attempted to find an efficient strategy with which to overcome it. In this study, we investigate the synergistic anticancer effects of resveratrol (RSV) and doxorubicin (Dox) against human breast cancer cell lines. Methods The synergistic effects of RSV on chemosensitivity were examined in Dox-resistant breast cancer (MCF-7/adr) and MDA-MB-231 cells. In vivo experiments were performed using a nude mouse xenograft model to investigate the combined sensitization effect of RSV and Dox. Results and conclusion RSV markedly enhanced Dox-induced cytotoxicity in MCF-7/adr and MDA-MB-231 cells. Treatment with a combination of RSV and Dox significantly increased the cellular accumulation of Dox by down-regulating the expression levels of ATP-binding cassette (ABC) transporter genes, MDR1, and MRP1. Further in vivo experiments in the xenograft model revealed that treatment with a combination of RSV and Dox significantly inhibited tumor volume by 60%, relative to the control group. General significance These results suggest that treatment with a combination of RSV and Dox would be a helpful strategy for increasing the efficacy of Dox by promoting an intracellular accumulation of Dox and decreasing multi-drug resistance in human breast cancer cells.
Databáze: OpenAIRE
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