Abstract 735
Background
Breast cancer is the most common cancer in women and its metastasis markedly exacerbates patients’ prognosis. In particular, triple negative breast cancer (TNBC), which lacks estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2), is an aggressive subtype of breast cancer frequently forming metastatic lesions. Differentiation-inducing factor-1 (DIF-1) identified in Dictyostelium discoideum inhibits cell proliferation and migration of various mammalian cancer cells. However, the effect of DIF-1 on TNBC has not been examined. Here, we investigated whether DIF-1 shows anti-proliferative and anti-metastatic effects on TNBC by in-vivo and in-vitro experiments.
Methods
In in-vivo experiments, we used cancer xenograft model mice in which murine TNBC 4T1/Luc cells (1.0 × 106 cells/mL) were injected into mammary fat pads to evaluate the effects of intragastric administration of DIF-1 (300 mg/kg/day) on the primary tumor growth and lung metastasis. In in-vitro experiments, we carried out assays for cell proliferation, migration and invasion to evaluate the anti-proliferative and anti-metastatic effects of DIF-1. We also conducted Western blotting and real-time RT-PCR to identify the mechanisms for DIF-1’s anti-cancer effects.
Results
In vivo, administration of DIF-1 significantly suppressed the primary tumor growth and lung metastasis without adverse effects such as weight loss and myelosuppression. In vitro, DIF-1 reduced cyclin D1 and c-Myc by inhibiting transcription and promoting degradation of the proteins, which resulted in the suppression of cell proliferation. DIF-1 also suppressed cell migration and invasion and reduced the protein expressions of snail, twist, vimentin and MMP-2, crucial factors in epithelial-mesenchymal transition (EMT).
Conclusions
DIF-1 exerts anti-cancer effects in TNBC by reducing cell cycle accelerators and reversing EMT. Our findings suggest that using DIF-1 as a lead compound could develop a novel anti-cancer agent for TNBC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The study protocol was approved by the Committee on Ethics of Animal Experiments of Kyushu University. Animal handling and procedures were carried out in compliance with the Guidelines for Animal Experiments, Kyushu University, and the Law (No. 105) and Notification (No. 6) of the Japanese Government.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
785 - JAK-STAT inhibitor overcomes interferon γ-reduced, NK cell-mediated cytotoxicity in non-small-cell lung cancer cells
Presenter: Riki Okita
Session: Poster Display session 1
Resources:
Abstract
2326 - Low LATS2 expression is associated with poor prognosis in non small cell lung cancer
Presenter: Si-hyong Jang
Session: Poster Display session 1
Resources:
Abstract
5960 - Application of ESCAT and OncoKB scales in Liquid biopsy (LB) in Advanced NSCLC patients (pts): Is it feasible and reliable?
Presenter: Michael McCusker
Session: Poster Display session 1
Resources:
Abstract
4855 - IDH1R132H mutation induces a less aggressive phenotype of glioma cells and affects the radiosensitivity by interacting with Wnt/β-catenin signaling
Presenter: Xuetao Han
Session: Poster Display session 1
Resources:
Abstract
2641 - Impact of Angiopoietin-2 on glioblastoma response to combined chemo-radiotherapy
Presenter: Charly Helaine
Session: Poster Display session 1
Resources:
Abstract
5743 - The Discovery of RNA-aptamers That Selectively Bind and Inhibit Glioblastoma Stem Cells by targeting EphA2
Presenter: Alessandra Affinito
Session: Poster Display session 1
Resources:
Abstract
4160 - Impact of tumor reoxygenation by nanoparticles on Tumor Associated Macrophages (TAMs)
Presenter: Aurélie Ferré
Session: Poster Display session 1
Resources:
Abstract
2474 - Prognostic significance of c-Rel/p50 heterodimer in the tumor microenvironment of uveal melanoma
Presenter: Seema Kashyap
Session: Poster Display session 1
Resources:
Abstract
1769 - Synergistic role of BAP1 and DNA damage response pathway in uveal melanoma and its prognostic significance.
Presenter: JAYANTI JHA
Session: Poster Display session 1
Resources:
Abstract
5037 - CXCR4, CCR2 and CCR5 expression in subsets of tumor cells with stem and/or EMT features
Presenter: Olga Savelieva
Session: Poster Display session 1
Resources:
Abstract