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Updated: Sep 16, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Gallium maltolate and cisplatin co-treatment effectively targets triple-negative breast cancer in spheroid and mouse
Ya-Wen Yang1, Yu-Chen Hsieh2, Ching-Yu Liu2
1Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Abstract:
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks targeted therapies and is characterized by high invasiveness and metastatic potential. Our previous work demonstrated that GaM (gallium maltolate) blocks cell cycle progression and impairs ribosomal synthesis in TNBC cells. Moreover, GaM treatment promotes ferroptosis activation, and its combination with cisplatin exhibits synergistic effects. To further evaluate the efficacy of these treatments, we applied them to three-dimensional spheroid and mouse models. Two types of spheroids were generated: one composed solely of TNBC cells (MDA-MB-231) and the other a co-culture with normal breast cells (MCF10A). In both MDA/MCF10A and MDA-MB-231 spheroids, we observed enhanced p53 activation and increased p21 expression, with the effects being more pronounced in the MDA-MB-231 spheroids. These effects were stronger with the combination treatment than with either treatment alone. Similar results were observed in a xenograft model, where tumors formed from MDA-MB-231 cells in nude mice. The combination therapy reduced tumor size to a similar extent as cisplatin alone and did not cause adverse effects in mice. The combination therapy induced apoptosis, nucleolar stress, and ferroptosis. Additionally, the treatment inhibited cell migration and metastasis - by increasing E-cadherin levels and reducing metalloproteases. These findings provide a strong foundation for further mechanistic studies and potential clinical applications.
Insights
Gallium maltolate (GaM) combined with cisplatin shows promise for triple-negative breast cancer (TNBC). This combination therapy effectively reduced tumor growth and metastasis in preclinical models, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies and exhibits aggressive behavior.
- Previous research indicated gallium maltolate (GaM) inhibits TNBC cell cycle and ribosomal synthesis, promoting ferroptosis.
- GaM and cisplatin demonstrated synergistic effects in preliminary studies.
Purpose of the Study:
- To evaluate the efficacy of GaM and cisplatin combination therapy in preclinical models of TNBC.
- To investigate the molecular mechanisms underlying the combination treatment's effects on TNBC cells and tumors.
Main Methods:
- Utilized three-dimensional TNBC spheroids (MDA-MB-231) and co-culture spheroids (MDA-MB-231/MCF10A).
- Administered GaM and cisplatin as single agents and in combination to spheroid and xenograft models in nude mice.
- Assessed molecular markers including p53, p21, E-cadherin, metalloproteases, apoptosis, and ferroptosis.
Main Results:
- Combination therapy significantly enhanced p53 activation and p21 expression in spheroids, particularly in TNBC-only spheroids.
- In vivo studies showed the combination therapy reduced tumor size, induced apoptosis, nucleolar stress, and ferroptosis.
- The treatment inhibited cell migration and metastasis by modulating E-cadherin and metalloprotease levels without observable adverse effects.
Conclusions:
- GaM and cisplatin combination therapy demonstrates significant preclinical efficacy against TNBC.
- The combined treatment targets multiple cancer hallmarks including proliferation, apoptosis, and metastasis.
- These findings support further investigation for clinical applications in TNBC treatment.
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