Intratumoral Treatment with 5-Androstene-3ß, 17a-Diol Reduces Tumor Size and Lung Metastasis in a Triple-Negative Experimental Model of Breast Cancer
Por:
Ruiz Manzano R.A., Nava-Castro K.E., Palacios-Arreola M.I., Hernández-Cervantes R., Del Río-Araiza V.H., Segovia-Mendoza M., Pérez-Torres A., Girón-Pérez M.I., Morales-Montor J.
Publicada:
1 ene 2022
Resumen:
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-3ß, 17a-diol (a-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 a-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 a-AED. In this sense, cells treated with higher doses (100 and 200 µM) showed an antiproliferative effect. The a-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 a-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 a-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of a-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 a-AED-treated mice. The above suggests that a-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies. © 2022 by the authors.
Filiaciones:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Grupo de Biología y Química Atmosférica, Departamento de Ciencias Ambientales, Instituto de Ciencias de la Atmósfera, y Cambio Climático, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Departamento de Parasitologia, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, 04510, Mexico
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, 04510, Mexico
Departamento de Biologia Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Edificio A, 4to Piso, Ciudad Universitaria, Ciudad de México, 04510, Mexico
Laboratorio Nacional para la Investigación en Inocuidad Alimentaria, Unidad Nayarit, Universidad Autónoma de Nayarit, Tepic, 63000, Mexico
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