Journal
AGING-US
Volume 13, Issue 3, Pages 3202-3217Publisher
IMPACT JOURNALS LLC
Keywords
GV1001; benign prostate hyperplasia; androgen receptor; dihydrotestosterone; epithelia-mesenchymal transition
Categories
Funding
- NRF of Korea [2017R1A2B2010948, 2017R1A6A3A11032576, 2020R 1C1C1009334]
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GV1001 effectively suppresses the proliferation of prostate cells, including stromal myofibroblasts and epithelial cells, by regulating cell growth and reducing hypertrophy. It also prevents prostatic fibrosis by inhibiting epithelial-mesenchymal transition through competing with testosterone for binding to androgen receptors, suggesting its potential as a therapeutic drug for BPH with fibrosis.
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)-beta, Snail, Slug, N-cadherin, and Vimentin, and by up-regulating E-cadherin. Taken together, these results suggest that GV1001, which suppresses TGF-beta-mediated EMT by outcompeting testosterone for binding to AR, is a potential therapeutic drug for BPH accompanied by prostatic fibrosis.
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