RT Journal Article
SR Electronic
T1 Transcriptome Analysis and In Vivo Activiy of Fluvastatin Versus Zoledronic Acid in a Murine Breast Cancer Metastasis Model
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.111.077248
DO 10.1124/mol.111.077248
A1 Nadejda Vintonenko
A1 Jean-Philippe Jais
A1 Nadim Kassis
A1 Mohamed Abdelkarim
A1 Gerard-Yves Perret
A1 Marc Lecouvey
A1 Michel Crepin
A1 Melanie Di Benedetto
YR 2012
UL http://molpharm.aspetjournals.org/content/early/2012/06/20/mol.111.077248.abstract
AB Statins and bisphosphonates (BPs) are two distinct classes of isoprenoid pathway inhibitors targeting downstream enzyme of HMG-CoA reductase (upstream enzyme) and Farnesyl-pyrophosphate synthase, respectively. Here, we studied Fluvastatin (Fluva) and Zoledronate (Zol), representative molecules of each class, respectively. In vivo metastatic potentials of both molecules were assessed. For the first time, we observed a significant reduction of established metastasis progression under Fluva treatment. Treatment with Zol at 100 μg/kg and Fluva at 15 mg/kg both inhibited 80% of metastasis bioluminescence signal and increased mice survival. The Zol and Fluva transcriptomic profiles of MDA-MB-231 treated cells, revealed analogous patterns of affected genes but each of them reached with different kinetics. The observable changes in gene expression started after 24 for Fluva IC5072h and only after 48h for Zol IC5072h. To obtain early changes in gene expression of Zol treated cells, three times higher dose of Zol IC5072h, had to be applied. Combining Fluva and Zol in vivo showed no synergy but a several days benefit in mice survival. This study demonstrated that Zol or Fluva are of potential clinical use for the treatment of established