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- Title
Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment.
- Authors
Goto, Wataru; Kashiwagi, Shinichiro; Asano, Yuka; Takada, Koji; Morisaki, Tamami; Takahashi, Katsuyuki; Fujita, Hisakazu; Shibutani, Masatsune; Amano, Ryosuke; Takashima, Tsutomu; Tomita, Shuhei; Hirakawa, Kosei; Ohira, Masaichi
- Abstract
<bold>Background: </bold>Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo.<bold>Methods: </bold>Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined.<bold>Results: </bold>Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone.<bold>Conclusions: </bold>Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.
- Subjects
HORMONE receptor positive breast cancer; TRIPLE-negative breast cancer; DEFEROXAMINE; BREAST cancer; IRON chelates; ERIBULIN
- Publication
BMC Cancer, 2020, Vol 20, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-020-07673-9