Antitumor activity of interferon-ß1a in hormone refractory prostate cancer with neuroendocrine differentiation.
J Endocrinol Invest
; 40(7): 761-770, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28247216
ABSTRACT
PURPOSE:
Type I interferons (IFN-α and IFN-ß) are a class of cytokines that exert several biological activities, such as modulation of cell proliferation and differentiation and of the immune system. Although these cytokines interact with a common receptor complex, IFN-ß showed a more potent antitumor activity than IFN-α in several tumor models. New recombinant human IFN-ß products, such as IFN-ß1a and IFN-ß1b, have been produced in order to improve the stability and bioavailability of natural IFN-ß. In this report, we analyzed the effects of recombinant IFN-ß1a on the cell proliferation of two human androgen-resistant prostate cancer cell lines with neuroendocrine differentiation (DU-145, PC-3) and related mechanisms of action.METHODS:
The effects of IFN-ß1a on the cell growth proliferation, cell cycle, and apoptosis have been evaluated in DU-145 and PC-3 cells through MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. Moreover, the expression of neuron-specific enolase (NSE), cleaved caspase-3, caspase-8, and PARP was evaluated through Western blotting.RESULTS:
IFN-ß1a showed a significant anti-proliferative activity in both androgen-resistant cell lines. This effect was related to cell cycle perturbation and induction in apoptosis, as shown by flow cytometric analysis, the activation of caspase-3 and caspase-8 and PARP cleavage during incubation with IFN-ß1a. Moreover, this cytokine reduced the expression of NSE in both cell lines.CONCLUSIONS:
Recombinant IFN-ß1a (Rebif) showed a potent in vitro anti-proliferative activity in androgen-resistant prostate cancer cells, and it could represent a promising tool for the treatment of this tumor.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Tumores Neuroendócrinos
/
Neoplasias de Próstata Resistentes à Castração
/
Interferon beta-1a
/
Antineoplásicos
Limite:
Humans
/
Male
Idioma:
En
Revista:
J Endocrinol Invest
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Itália