Different statins produce highly divergent changes in gene expression profiles of human hepatoma cells: a pilot study

Acta Biochim Pol. 2011;58(4):635-9. Epub 2011 Nov 30.

Abstract

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the sterol biosynthesis pathway. Statin therapy is commonly regarded as well tolerated. However, serious adverse effects have also been reported, especially during high-dose statin therapy. The aim of our study was to investigate the effect of statins on gene expression profiles in human hepatoma HepG2 cells using Affymetrix Human Genome U133 Plus 2.0 arrays. Expression of 102, 857 and 1091 genes was changed substantially in HepG2 cells treated with simvastatin, fluvastatin and atorvastatin, respectively. Pathway and gene ontology analysis showed that many of the genes with changed expression levels were involved in a broad range of metabolic processes. The presented data clearly indicate substantial differences between the tested statins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atorvastatin
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Computational Biology
  • Fatty Acids, Monounsaturated / pharmacology
  • Fluvastatin
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects*
  • Genome, Human
  • Hep G2 Cells
  • Heptanoic Acids / pharmacology
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Indoles / pharmacology
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / genetics
  • Mevalonic Acid / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pilot Projects
  • Principal Component Analysis
  • Pyrroles / pharmacology
  • Simvastatin / pharmacology

Substances

  • Fatty Acids, Monounsaturated
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Pyrroles
  • Fluvastatin
  • Atorvastatin
  • Simvastatin
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases
  • Mevalonic Acid