Consecutive salinomycin treatment reduces doxorubicin resistance of breast tumor cells by diminishing drug efflux pump expression and activity

  • Authors:
    • Adam Hermawan
    • Ernst Wagner
    • Andreas Roidl
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  • Published online on: December 22, 2015     https://doi.org/10.3892/or.2015.4509
  • Pages: 1732-1740
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Abstract

Chemoresistance is a major challenge for the successful therapy of breast cancer. The discovery of salinomycin as an anticancer stem cell drug provides progress in overcoming chemoresistance. However, it remains to be elucidated whether salinomycin treatment is able to sensitize cancer cells to chemotherapeutic drugs. In the present study, we consecutively treated epithelial MCF-7 and BT-474 breast cancer cells as well as mesenchymal MDA-MB 231 and MDA-MB 436 cells with salinomycin, and analyzed the gene expression of the two prominent multiple drug resistance (MDR) genes, MDR1 and BCRP1. We found that repeated treatment with salinomycin generated resistance against this drug in all cell lines and increased the chemosensitivity towards doxorubicin. Drug efflux pump gene expression and pump activity of MDR1 and BCRP1 were downregulated in almost all cell lines, except for MDR1 in the MDA-MB 231 cells. Consequently, the intracellular doxorubicin accumulation was increased compared to the respective parental cells. Our findings suggest a novel treatment option for MDR tumors by sensitizing these tumors via salinomycin pretreatment.
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March-2016
Volume 35 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Hermawan A, Wagner E and Roidl A: Consecutive salinomycin treatment reduces doxorubicin resistance of breast tumor cells by diminishing drug efflux pump expression and activity. Oncol Rep 35: 1732-1740, 2016
APA
Hermawan, A., Wagner, E., & Roidl, A. (2016). Consecutive salinomycin treatment reduces doxorubicin resistance of breast tumor cells by diminishing drug efflux pump expression and activity. Oncology Reports, 35, 1732-1740. https://doi.org/10.3892/or.2015.4509
MLA
Hermawan, A., Wagner, E., Roidl, A."Consecutive salinomycin treatment reduces doxorubicin resistance of breast tumor cells by diminishing drug efflux pump expression and activity". Oncology Reports 35.3 (2016): 1732-1740.
Chicago
Hermawan, A., Wagner, E., Roidl, A."Consecutive salinomycin treatment reduces doxorubicin resistance of breast tumor cells by diminishing drug efflux pump expression and activity". Oncology Reports 35, no. 3 (2016): 1732-1740. https://doi.org/10.3892/or.2015.4509