Combination of Lipitor and Celebrex inhibits prostate cancer VCaP cells in vitro and in vivo

Anticancer Res. 2014 Jul;34(7):3357-63.

Abstract

Background/aim: Lipitor is a cholesterol-lowering drug and Celebrex is a Cyclooxygenase-2 inhibitor. We investigated the effects of Lipitor and Celebrex on human prostate cancer VCaP cells cultured in vitro and grown as orthotopic xenograft tumors in SCID mice.

Materials and methods: Apoptosis was measured by morphological assessment and caspase-3 assay. Nuclear factor-kappa B (NF-κB) activation was determined by luciferase reporter assay. B-cell lymphoma-2 (Bcl2) was measured by western blotting and immunohistochemistry. Orthotopic prostate tumors were monitored by the IVIS imaging system.

Results: the combination of Lipitor and Celebrex had stronger effects on the growth and apoptosis of VCaP cells than did either drug alone. The combination more potently inhibited activation of NFκB and expression of Bcl2 than either drug alone. The growth of orthotopic VCaP prostate tumors was strongly inhibited by treatment with the drug combination.

Conclusion: Administration of Lipitor and Celebrex in combination may be an effective strategy for inhibiting the growth of prostate cancer.

Keywords: NFκB; NSAIDs; Prostate cancer; orthotopic; statin.

Publication types

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

MeSH terms

  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Atorvastatin
  • Celecoxib
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / pharmacology*
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacology*
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Anticholesteremic Agents
  • Cyclooxygenase 2 Inhibitors
  • Heptanoic Acids
  • Pyrazoles
  • Pyrroles
  • Sulfonamides
  • Atorvastatin
  • Celecoxib