title: Fulvestrant reverses doxorubicin resistance in multidrug-resistant breast cell lines independent of estrogen receptor expression.
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.
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Donghai
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Center for Cancer Biology and Innovative Therapeutics, Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Sui
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D065171:Estrogen Receptor Antagonists; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D004317:Doxorubicin