Effects of simvastatin and rosuvastatin on RAS protein, matrix metalloproteinases and NF-κB in lung cancer and in normal pulmonary tissues

Cell Prolif. 2013 Apr;46(2):172-82. doi: 10.1111/cpr.12018.

Abstract

Objectives: In this study, we have evaluated effects of 24-hour treatments with simvastatin or rosuvastatin on RAS protein, NF-κB and MMP expression in LC tissues obtained from 12 patients undergoing thoracic surgery.

Materials and methods: Normal and lung tumour tissues obtained from each sample were exposed to simvastatin (2.5-30 μm) or rosuvastatin (1.25-30 μm) and western blot analysis was then performed.

Results: We documented increased expression of proteins, MMP-2, MMP-9 and NF-κB-p65 in LC tissues, with respect to normal tissues (P < 0.01). In the malignant tissues, simvastatin and rosuvastatin significantly (P < 0.01) and dose-dependently reduced RAS protein, MMP-2/9 and NF-κB-p65 expression.

Conclusions: In conclusion, our results suggest that simvastatin and rosuvastatin could play a role in LC treatment by modulation of RAS protein, MMP-2/9 and NF-κB-p65.

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Aged
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Female
  • Fluorobenzenes / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Pyrimidines / pharmacology*
  • Rosuvastatin Calcium
  • Simvastatin / pharmacology*
  • Smoking / adverse effects
  • Sulfonamides / pharmacology*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*
  • Tumor Cells, Cultured
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Fluorobenzenes
  • Pyrimidines
  • RELA protein, human
  • Sulfonamides
  • Transcription Factor RelA
  • Rosuvastatin Calcium
  • Simvastatin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • ras Proteins