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


Salis O., Okuyucu A., Bedir A., Gor U., Kulcu C., Yenen E., ...More

TUMOR BIOLOGY, vol.37, no.3, pp.3017-3024, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 3
  • Publication Date: 2016
  • Doi Number: 10.1007/s13277-015-4119-2
  • Journal Name: TUMOR BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3017-3024
  • Keywords: Migration, Fluvastatin, RTCA, MCF-7, Hep3B, SGK1, EPITHELIAL-MESENCHYMAL TRANSITION, ACTIVATED PROTEIN-KINASE, GROWTH-FACTOR-BETA, SUPPRESSOR GENE, EXPRESSION, CANCER, SERUM, OVEREXPRESSION, METASTASIS, MECHANISMS
  • Ondokuz Mayıs University Affiliated: Yes

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-beta 1 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-beta(1) and combinations of TGF-beta(1)/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-beta 1 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.