4.4 Article

Downregulation of lysine-specific demethylase 1 enhances the sensitivity of hormone-sensitive prostate cancer cells to androgen deprivation therapy

Journal

ONCOLOGY LETTERS
Volume 21, Issue 2, Pages -

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2020.12354

Keywords

LSD1; androgen deprivation therapy; hormone-sensitive prostate cancer; apoptosis

Categories

Funding

  1. National Natural Science Foundation of China [81972408]
  2. Province Natural Science Foundation of Hubei [2016CFB 114, 2019CFB302]
  3. Science Foundation of Wuhan [20150601010100 49]
  4. Application and Basic Research Project Of Wuhan City [2018060401011321]
  5. Fundamental Research Funds for the Central Universities [2042017kf0089]

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Downregulation of LSD1 impairs the proliferation and invasiveness of PCa cells, enhances ADT-induced apoptosis, and effectively enhances the efficacy of ADT for hormone-sensitive PCa, making it a promising adjunctive therapy for this disease.
Lysine-specific demethylase 1 (LSD1) plays an important role in androgen receptor (AR) signaling, and LSD1 levels are associated with prostate cancer (PCa) progression. The present study investigated the association between the downregulation of LSD1 and the proliferation and invasiveness of PCa cells, as well as the effect of LSD1 on the androgen deprivation therapy (ADT)-induced apoptosis of PCa cells. The effect of the inhibition of LSD1 combined with ADT on PCa cell apoptosis was characterized. Furthermore, the mechanisms underlying LSD1-mediated apoptosis induced by ADT in PCa cells were investigated. Downregulation of LSD1 impaired the proliferation and invasiveness of PCa cells. Moreover, downregulation of LSD1 enhanced the apoptosis of PCa cells induced by bicalutamide in vitro. Downregulation of LSD1 decreased PSA expression, increased caspase 3 and Bax expression, decreased Bcl-2 expression and consequently enhanced castration-induced PCa cell apoptosis in vivo. These findings indicated that downregulation of LSD1 could effectively enhance the efficacy of ADT for hormone- sensitive PCa, demonstrating that this could be a promising adjunctive therapy with ADT for this disease.

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