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Updated: Feb 3, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Signaling pathway inhibitors target breast cancer stem cells in triple-negative breast cancer
Wenlong Li1, Hongmei Yang1, Xiaoli Li2
1Department of Breast Surgery, The First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Abstract:
The present study aimed to investigate the efficacy of five signaling pathway inhibitors, N-[N-(3,5‑difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, vismodegib, salinomycin, ruxolitinib and stattic, as novel therapeutic agents that target breast cancer stem cells (BCSCs) in triple-negative breast cancer (TNBC). The in vitro anti-proliferative, anti-invasive, pro-apoptotic and inhibitory effects on BCSC self-renewal of these signaling pathway inhibitors on the TNBC stem cell line HCC38 were examined by MTT assays, Matrigel invasion assays, flow cytometry and suspension mammosphere assays, respectively. For the in vivo study, another TNBC stem cell line, HCC1806, pretreated with these signaling pathway inhibitors, was inoculated into female nonobese diabetic/severe combined immunodeficient mice, and the tumor volumes were measured following tumor formation. Treatment of HCC38 cells with each signaling pathway inhibitor significantly decreased TNBC cell proliferation, cell invasion and mammosphere formation while inducing cell apoptosis by inhibiting the protein expression or phosphorylation of downstream signaling molecules. In the xenograft mouse models, tumor formation and growth of HCC1806 cells pretreated with each signaling pathway inhibitor were effectively suppressed. Treatment with these signaling pathway inhibitors may provide a novel therapeutic strategy against TNBC by targeting BCSCs, thus providing promising insight for clinical applications in patients with TNBC.
Insights
Five signaling pathway inhibitors show promise in targeting breast cancer stem cells (BCSCs) for triple-negative breast cancer (TNBC) treatment. These agents reduced tumor growth and spread in preclinical models, offering new therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Breast cancer stem cells (BCSCs) are implicated in tumor recurrence and metastasis.
- Targeting BCSCs offers a promising strategy for effective TNBC treatment.
Purpose of the Study:
- To evaluate the efficacy of five signaling pathway inhibitors as novel therapeutic agents against BCSCs in TNBC.
- To investigate the in vitro and in vivo effects of these inhibitors on TNBC cell proliferation, invasion, apoptosis, and self-renewal.
- To explore the potential of these inhibitors for clinical application in TNBC patients.
Main Methods:
- In vitro studies utilized MTT assays, Matrigel invasion assays, flow cytometry, and mammosphere assays on the HCC38 TNBC stem cell line.
- In vivo studies involved xenograft mouse models using the HCC1806 TNBC stem cell line.
- Assessment of protein expression and phosphorylation of downstream signaling molecules was performed.
Main Results:
- Signaling pathway inhibitors significantly reduced TNBC cell proliferation, invasion, and mammosphere formation in vitro.
- These agents induced apoptosis in TNBC cells by inhibiting key signaling molecules.
- In vivo studies demonstrated effective suppression of tumor formation and growth in xenograft models.
Conclusions:
- The investigated signaling pathway inhibitors demonstrate significant potential as novel therapeutic agents targeting BCSCs in TNBC.
- These findings suggest a promising therapeutic strategy for TNBC by targeting BCSCs.
- The study provides valuable insights for potential clinical applications in TNBC treatment.
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