Effects of cisplatin on the LSD1-mediated invasion and metastasis of prostate cancer cells

Mol Med Rep. 2016 Sep;14(3):2511-7. doi: 10.3892/mmr.2016.5571. Epub 2016 Jul 28.

Abstract

Prostate cancer poses a major public health problem in men. Metastatic prostate cancer is incurable, and ultimately threatens the life of patients. Lysine‑specific demethylase 1 (LSD1) is an androgen receptor‑interacting protein that exerts a key role in regulating gene expression and is involved in numerous biological processes associated with prostate cancer. Cisplatin, also known as cis‑diamminedichloroplatinum or DDP, is a standard chemotherapeutic agent used to treat prostate cancer; however, it has the disadvantage of various serious side effects. The present study aimed to investigate the effects of LSD1 knockdown, and the interplay between LSD1 and DDP, on prostate cancer cell proliferation, apoptosis and invasion, and, therefore, the potential of LSD1 as a target for prostate cancer therapy. Flow cytometric analysis, Cell Counting kit 8 assay, Transwell assay and western blotting results revealed that LSD1 knockdown, in combination with DDP treatment, exerted antiproliferative, proapoptotic and anti‑invasive effects on PC3 prostate cancer cells. In addition, knockdown of LSD1 acted synergistically with DDP, thereby enhancing the induction of apoptosis, and the inhibition of proliferation and invasion in prostate cancer cells. These results indicated that LSD1 may serve as a potential therapeutic target, and may enhance the sensitivity of PC3 cells to DDP.

Publication types

  • Retracted Publication

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cisplatin / pharmacology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Knockdown Techniques
  • Histone Demethylases / genetics*
  • Histone Demethylases / metabolism
  • Humans
  • Male
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Antineoplastic Agents
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Histone Demethylases
  • KDM1A protein, human
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Cisplatin