Inhibition of Survivin Is Associated with Zoledronic Acid-induced Apoptosis of Prostate Cancer Cells

Anticancer Res. 2016 Mar;36(3):913-20.

Abstract

Background/aim: Evidence suggests that zoledronic acid (ZA) exerts direct antitumor effects on cancer cells but the underlying mechanisms of these actions are unknown. This study investigated the possible involvement of survivin in the antiproliferative effects of ZA in prostate cancer.

Materials and methods: 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye reduction assay was used to assess cell viability and acridine orange/ethidium bromide double staining to analyze cell death. Human Apoptosis Array evaluated the expression of apoptosis-related proteins. Survivin protein was measured by western blot technique and miR-203 levels were quantified by quantitative real-time polymerase chain reaction.

Results: ZA induced inhibition of cell proliferation and apoptosis activation, with down-regulation of survivin protein. A negative regulation at gene expression level may be hypothesized because we observed a significant decrease of survivin mRNA level and an increase of miR-203 expression after ZA exposure.

Conclusion: This study provides evidence that ZA may directly inhibit cancer cell proliferation, identifying survivin as one of its downstream targets.

Keywords: Prostate cancer; apoptosis; miR-203; survivin; zoledronic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Diphosphonates / pharmacology*
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Imidazoles / pharmacology*
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Male
  • MicroRNAs / genetics*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Survivin
  • Zoledronic Acid

Substances

  • BIRC5 protein, human
  • Diphosphonates
  • Imidazoles
  • Inhibitor of Apoptosis Proteins
  • MIRN203 microRNA, human
  • MicroRNAs
  • Survivin
  • Zoledronic Acid