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BioMed Research International - Volume 2014 2014, Article ID 532161, 10 pages -

Research Article

Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 50006, Taiwan

Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 40402, Taiwan

School of Pharmacy, China Medical University, Taichung 40402, Taiwan

Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua 50006, Taiwan

Received 14 May 2014; Revised 17 June 2014; Accepted 19 June 2014; Published 16 July 2014

Academic Editor: Shun-Fa Yang

Copyright © 2014 Dar-Ren Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Triple negative breast cancer TNBC is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to this agent is common. In some drug-resistant cells, drug efflux is mediated by adenosine triphosphate-dependent membrane transporter termed adenosine triphosphate-binding cassette ABC transporter, which can drive the substrates across membranes against concentration gradient. In the tumor microenvironment, upon interaction with mesenchymal stem cells MSCs, tumor cells exhibit altered biological functions of certain gene clusters, hence increasing stemness of tumor cells, migration ability, angiogenesis, and drug resistance. In our present study, we investigated the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon exposure of TNBC to MSC-secreted conditioned medium CM, noticeable drug resistance against doxorubicin with markedly increased BCRP protein expression was observed. Intracellular doxorubicin accumulation of TNBC was also decreased by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the list of potential targets for overcoming drug resistance induced by MSCs in TNBC patients.

Autor: Dar-Ren Chen, Dah-Yuu Lu, Hui-Yi Lin, and Wei-Lan Yeh



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