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 |
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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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