Antimetastatic effect of fluvastatin on breast and hepatocellular carcinoma cells in relation to SGK1 and NDRG1 genes

Tumour Biol. 2016 Mar;37(3):3017-24. doi: 10.1007/s13277-015-4119-2. Epub 2015 Sep 29.

Abstract

Metastasis occurs due to migration of the cells from primary tumor toward other tissues by gaining invasive properties. Since metastatic invasion shows a strong resistance against conventional cancer treatments, the studies on this issue have been focused. Within this context, inhibition of migration and determination of the relationships at the gene level will contribute to treatment of metastatic cancer cases. We have aimed to demonstrate the impact of TGF-β1 and fluvastatin on human breast cancer (MCF-7) and human hepatocellular carcinoma (Hep3B) cell cultures via Real-Time Cell Analyzer (RTCA) and to test the expression levels of some genes (NDRG1, SGK1, TWIST1, AMPKA2) and to compare their gene expression levels according to RTCA results. Both of cell series were applied TGF-β1 and combinations of TGF-β1/fluvastatin. Primer and probes were synthesized using Universal Probe Library (UPL, Roche) software, and expression levels of genes were tested via qPCR using the device LightCycler 480 II (Roche). Consequently, fluvastatin dose-dependently inhibited migration induced by TGF-β1 in both groups. This inhibition was accompanied by low level of SGK1 messenger RNA (mRNA) and high levels of NDRG1 and AMPKA2 mRNA. Thus, we conclude that fluvastatin plays an important role in reducing resistance to chemotherapeutics and preventing metastasis.

Keywords: Fluvastatin; Hep3B; MCF-7; Migration; RTCA; SGK1.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Movement / drug effects
  • Fatty Acids, Monounsaturated / pharmacology*
  • Female
  • Fluvastatin
  • Humans
  • Immediate-Early Proteins / genetics*
  • Indoles / pharmacology*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • MCF-7 Cells
  • Neoplasm Metastasis / prevention & control*
  • Nuclear Proteins / genetics
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Messenger / analysis
  • Transforming Growth Factor beta1 / pharmacology
  • Twist-Related Protein 1 / genetics

Substances

  • Cell Cycle Proteins
  • Fatty Acids, Monounsaturated
  • Immediate-Early Proteins
  • Indoles
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • Nuclear Proteins
  • RNA, Messenger
  • TWIST1 protein, human
  • Transforming Growth Factor beta1
  • Twist-Related Protein 1
  • Fluvastatin
  • PRKAA2 protein, human
  • Protein Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • AMP-Activated Protein Kinases