RESUMO
Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are highly aggressive neoplastic diseases that share numerous characteristics. In IBC and IMC, chemotherapy produces a limited pathological response and anti-androgen therapies have been of interest for breast cancer treatment. Therefore, the aim was to evaluate the effect of a therapy based on bicalutamide, a non-steroidal anti-androgen, with doxorubicin and docetaxel chemotherapy on cell proliferation, migration, tumor growth, and steroid-hormone secretion. An IMC-TN cell line, IPC-366, and an IBC-TN cell line, SUM149, were used. In vitro assays revealed that SUM149 exhibited greater sensitivity, reducing cell viability and migration with all tested drugs. In contrast, IPC-366 exhibited only significant in vitro reductions with docetaxel as a single agent or in different combinations. Decreased estrogen levels reduced in vitro tumor growth in both IMC and IBC. Curiously, doxorubicin resulted in low efficacy, especially in IMC. In addition, all drugs reduced the tumor volume in IBC and IMC by increasing intratumoral testosterone (T) levels, which have been related with reduced tumor progression. In conclusion, the addition of bicalutamide to doxorubicin and docetaxel combinations may represent a potential treatment for IMC and IBC.
Assuntos
Anilidas , Proliferação de Células , Docetaxel , Neoplasias Inflamatórias Mamárias , Neoplasias Mamárias Animais , Nitrilas , Compostos de Tosil , Compostos de Tosil/farmacologia , Humanos , Animais , Feminino , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Linhagem Celular Tumoral , Anilidas/farmacologia , Cães , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Neoplasias Inflamatórias Mamárias/patologia , Neoplasias Inflamatórias Mamárias/metabolismo , Proliferação de Células/efeitos dos fármacos , Docetaxel/farmacologia , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Animais/metabolismo , Doxorrubicina/farmacologia , Camundongos , Sobrevivência Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , TestosteronaRESUMO
The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no overexpression of HER-2. However, TNBC can express the androgen receptor (AR) or estrogen receptor ß (ERß). Also, TNBC secretes steroid hormones and is influenced by hormonal fluctuations, so the steroid inhibition could exert a beneficial effect in TNBC treatment. The aim of this study was to evaluate the effect of dutasteride, anastrozole and ASP9521 in in vitro processes using human TNBC cell lines. For this, immunofluorescence, sensitivity, proliferation and wound healing assays were performed, and hormone concentrations were studied. Results revealed that all TNBC cell lines expressed AR and ERß; the ones that expressed them most intensely were more sensitive to antihormonal treatments. All treatments reduced cell viability, highlighting MDA-MB-453 and SUM-159. Indeed, a decrease in androgen levels was observed in these cell lines, which could relate to a reduction in cell viability. In addition, MCF-7 and SUM-159 increased cell migration under treatments, increasing estrogen levels, which could favor cell migration. Thus, antihormonal treatments could be beneficial for TNBC therapies. This study clarifies the importance of steroid hormones in AR and ERß-positive cell lines of TNBC.
Assuntos
Androgênios , Neoplasias de Mama Triplo Negativas , Humanos , Androgênios/farmacologia , Receptores de Estrogênio , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Linhagem Celular Tumoral , Estrogênios/farmacologia , Receptores Androgênicos/metabolismo , Esteroides/farmacologia , Receptor alfa de Estrogênio , Proliferação de CélulasRESUMO
Trabajo descriptivo y cualitativo con el objeto de reconocer las actitudes maternas con relación al Programa Ampliado de Vacunación (PAI)