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Updated: Aug 25, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Intratumoral Treatment with 5-Androstene-3β, 17α-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative
Rocío Alejandra Ruiz Manzano1, Karen Elizabeth Nava-Castro2, Margarita Isabel Palacios-Arreola2
1Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico.
Abstract:
Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3β, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 μM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.
Insights
Androstene-3β, 17α-diol (α-AED) shows promise as a breast cancer treatment. Intratumoral administration of α-AED reduced tumor growth and metastasis in mice, suggesting potential for clinical trials.
Area of Science:
- Oncology
- Endocrinology
- Immunology
Background:
- Breast cancer treatment failure is a significant challenge due to low response rates, high costs, and toxicities.
- Novel therapeutic strategies are needed to improve treatment efficacy and reduce adverse effects.
- Androstene-3β, 17α-diol (α-AED) is a steroid with demonstrated antiproliferative effects on breast tumor cells.
Purpose of the Study:
- To investigate the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model.
- To evaluate the potential of α-AED as a less toxic and more effective breast cancer treatment.
- To assess the impact of α-AED on tumor cell proliferation, immune cell infiltration, and angiogenesis.
Main Methods:
- In vitro studies using mouse and human mammary tumor cells treated with varying doses of α-AED.
- In vivo studies involving intratumoral administration of α-AED in a mouse model of triple-negative breast cancer.
- Analysis of tumor weight, immune cell populations (NK cells, plasmablasts), VEGF levels, and systemic anti-tumor IgG concentration.
Main Results:
- α-AED exhibited a biphasic effect in vitro, with higher doses (100 and 200 μM) showing antiproliferative activity.
- Intratumoral α-AED administration significantly reduced average tumor weight in mice.
- α-AED treatment increased NK cells and plasmablasts within tumors and decreased VEGF levels, correlating with reduced metastasis.
Conclusions:
- α-AED demonstrates significant anti-tumor effects in a preclinical model of triple-negative breast cancer.
- Local administration of α-AED reduces tumor growth and may inhibit metastasis by lowering VEGF levels.
- α-AED holds potential as an alternative or adjuvant therapy for breast cancer, warranting further clinical investigation.
