GV1001 interacts with androgen receptor to inhibit prostate cell proliferation in benign prostatic hyperplasia by regulating expression of molecules related to epithelial-mesenchymal transition.
Aging (Albany NY)
; 13(3): 3202-3217, 2021 02 04.
Article
em En
| MEDLINE
| ID: mdl-33539321
ABSTRACT
Prostate cell proliferation, driven by testosterone, is a major characteristic of benign prostatic hyperplasia (BPH). GV1001, a human telomerase reverse transcriptase catalytic subunit, is an injectable formulation used as a cancer vaccine. It functions as a cell penetrating peptide to regulate cell proliferation. Here, we found that GV1001 effectively suppressed proliferation of prostatic stromal myofibroblasts (WPMY-1) and prostatic epithelial cells (RWPE-1 and WPE-NA22) treated with dihydrotestosterone. Also, GV1001 bound to androgen receptors (ARs) in the cytosol of stromal and epithelial cells. In an experimental animal model implanted with an infusion pump for spontaneous and continuous release of testosterone, revealed that GV1001 reduced prostatic hypertrophy and inhibited the cell proliferation and the expression of Ki67, proliferating cell nuclear antigen, and prostate specific antigen. In addition, GV1001 prevented fibrosis of the prostate by downregulating expression of prostatic epithelial-mesenchymal transition (EMT)-related proteins such as transforming growth factor (TGF)-ß, Snail, Slug, N-cadherin, and Vimentin, and by up-regulating E-cadherin. Taken together, these results suggest that GV1001, which suppresses TGF-ß-mediated EMT by outcompeting testosterone for binding to AR, is a potential therapeutic drug for BPH accompanied by prostatic fibrosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Hiperplasia Prostática
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Receptores Androgênicos
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Telomerase
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Proliferação de Células
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Transição Epitelial-Mesenquimal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Aging (Albany NY)
Assunto da revista:
GERIATRIA
Ano de publicação:
2021
Tipo de documento:
Article