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Oncol Rep. 2017 Feb;37(2):705-712. doi: 10.3892/or.2016.5315. Epub 2016 Dec 14.

Fulvestrant reverses doxorubicin resistance in multidrug-resistant breast cell lines independent of estrogen receptor expression.

Author information

1
Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
2
Program of Innovative Cancer Therapeutics, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China.
3
Center for Cancer Biology and Innovative Therapeutics, Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.

Abstract

Drug resistance, a major obstacle to successful cancer chemotherapy, frequently occurs in recurrent or metastatic breast cancer and results in poor clinical response. Fulvestrant is a new type of selective estrogen receptor (ER) downregulator and a promising endocrine therapy for breast cancer. In this study, we evaluated the combination treatment of fulvestrant and doxorubicin in ER-negative multidrug-resistant (MDR) breast cancer cell lines Bads‑200 and Bats‑72. Fulvestrant potentiated doxorubicin-induced cytotoxicity, apoptosis and G2/M arrest with upregulation of cyclin B1. It functioned as a substrate for P-glycoprotein (P-gp) without affecting its expression. Furthermore, fulvestrant not only restored the intracellular accumulation of doxorubicin but also relocalized it to the nuclei in Bats‑72 and Bads‑200 cells, which may be another potential mechanism of reversal of P-gp mediated doxorubicin resistance. These results indicated that the combination of fulvestrant and doxorubicin-based chemotherapy may be feasible and effective for patients with advanced breast cancer.

PMID:
28000875
PMCID:
PMC5355712
DOI:
10.3892/or.2016.5315
[Indexed for MEDLINE]
Free PMC Article

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