Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin.
Biochim Biophys Acta. 2014 Jan; 1840(1):615-25.BB

Abstract

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.

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Authors+Show Affiliations

Kim TH
Laboratory of Molecular Toxicology, College of Pharmacy, Pusan National University, San 30, Jangjeon-dong, Geumjeung-gu, Busan 609-735, Republic of Korea; Division of Toxicology, College of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
Shin YJ
No affiliation info available
Won AJ
No affiliation info available
Lee BM
No affiliation info available
Choi WS
No affiliation info available
Jung JH
No affiliation info available
Chung HY
No affiliation info available
Kim HS
No affiliation info available

MeSH

ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1AnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBlotting, WesternBreast NeoplasmsCell ProliferationDoxorubicinDrug Resistance, MultipleDrug Resistance, NeoplasmDrug SynergismFemaleHumansMiceMice, Inbred BALB CMultidrug Resistance-Associated ProteinsRNA, MessengerReal-Time Polymerase Chain ReactionResveratrolReverse Transcriptase Polymerase Chain ReactionStilbenesTissue DistributionTumor Cells, Cultured

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24161697