Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells 
via decreased efflux of doxorubicin

Kim,Kwang‑Youn; Kim,Sang‑Hun; Yu,Sun‑Nyoung; Park,Suel‑Ki; Choi,Hyeun‑Deok; Yu,Hak‑Sun; Ji,Jae‑Hoon; Seo,Young‑Kyo; Ahn,Soon‑Cheol

doi:10.3892/mmr.2015.3633

Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin

Authors:
- Kwang‑Youn Kim
- Sang‑Hun Kim
- Sun‑Nyoung Yu
- Suel‑Ki Park
- Hyeun‑Deok Choi
- Hak‑Sun Yu
- Jae‑Hoon Ji
- Young‑Kyo Seo
- Soon‑Cheol Ahn
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Affiliations: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea, Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 626‑870, Republic of Korea, Genome Instability Research Center, Ajou University School of Medicine, Suwon, Gyeonggi-do 443‑721, Republic of Korea, School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 689‑798, Republic of Korea
Published online on: April 16, 2015 https://doi.org/10.3892/mmr.2015.3633
Pages: 1898-1904
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Salinomycin is a monocarboxylic polyether antibiotic, which is widely used as an anticoccidial agent. The anticancer property of salinomycin has been recognized and is based on its ability to induce apoptosis in human multidrug resistance (MDR). The present study investigated whether salinomycin reverses MDR towards chemotherapeutic agents in doxorubicin‑resistant MCF‑7/MDR human breast cancer cells. The results demonstrated that doxorubicin‑mediated cytotoxicity was significantly enhanced by salinomycin in the MCF‑7/MDR cells, and this occurred in a dose‑dependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycin‑treated cells were higher compared with the cells treated with doxorubicin alone. In addition, flow cytometric analysis revealed that salinomycin significantly increased the net cellular uptake and decreased the efflux of doxorubicin. The expression levels of MDR‑1 and MRP‑1 were not altered at either the mRNA or protein levels in the cells treated with salinomycin. These results indicated that salinomycin was mediated by its ability to increase the uptake and decrease the efflux of doxorubicin in MCF‑7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapy.

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