Mechanistic Study of Inhibitory Effects of Atorvastatin and Docetaxel in Combination on Prostate Cancer

Cancer Genomics Proteomics. Mar-Apr 2016;13(2):151-60.

Abstract

Aim: To investigate the effects and mechanisms of docetaxel and atorvastatin administered individually or in combination on prostate cancer cells.

Materials and methods: Cell growth and apoptosis were determined by the trypan blue exclusion assay and morphological assessment of cells was performed with propidium iodide. NF-κB activity was determined by luciferase reporter gene assay and the western blot assay was used to determine the levels of Bcl-2, phospho-Akt, VEGF, and phospho-Erk1/2.

Results: Results showed that following pre-treatment with cholesterol, resistance of PC-3 prostate cancer cells to docetaxel was increased. The combination of docetaxel with atorvastatin potently inhibited growth and induced apoptosis in PC-3 cells. Mechanistic studies indicated that induction of apoptosis in PC-3 cells was associated with significant decreases in the levels of Bcl-2, VEGF, phosphor-Akt, and phosphor-Erk1/2.

Conclusion: Treatment with cholesterol decreased the sensitivity of prostate cancer cells to docetaxel. Docetaxel in combination with cholesterol-lowering drugs such as atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer.

Keywords: Combination treatment; atorvastatin; docetaxel; prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis
  • Atorvastatin / administration & dosage
  • Atorvastatin / therapeutic use*
  • Cell Line, Tumor
  • Cholesterol / pharmacology
  • Docetaxel
  • Drug Synergism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • NF-kappa B / genetics
  • Phosphorylation / drug effects
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Taxoids / administration & dosage
  • Taxoids / therapeutic use*
  • Transcription, Genetic

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • NF-kappa B
  • Taxoids
  • Docetaxel
  • Cholesterol
  • Atorvastatin