Title of article :
Statins potentiate cytostatic/cytotoxic activity of sorafenib but not sunitinib against tumor cell lines in vitro
Author/Authors :
Bil، نويسنده , , Jacek and Zapala، نويسنده , , Lukasz and Nowis، نويسنده , , Dominika and Jakobisiak، نويسنده , , Marek and Golab، نويسنده , , Jakub، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2010
Abstract :
The aim of this study was to investigate the potential cytostatic/cytotoxic effects of HMG-CoA reductase inhibitors and two orphan drugs registered for the treatment of advanced renal cell carcinoma, i.e. sorafenib and sunitinib against several different tumor cell lines. Cytostatic/cytotoxic effects were measured using crystal violet or MTT reduction assays. Cell cycle regulation was investigated using flow cytometry and Western blotting. The combination of lovastatin and sorafenib (but not sunitinib) produced synergistic cytostatic/cytotoxic effects against all tested tumor cell lines. In this study, an impairment of the protein prenylation, especially geranylgeranylation, resulted predominantly in the potentiation of the cytostatic/cytotoxic activity of sorafenib, in cell cycle arrest in G1 phase, and, in poor induction of apoptosis. Moreover, due to the fact that it has been well documented that sorafenib compromises the heart function, we studied the interaction of lovastatin and sorafenib using rat cardiomyoblast line H9c2. The combination showed strong synergistic cardiotoxic effects. Statins and tyrosine kinase inhibitors were used at doses that are achievable clinically, which makes the combination promising for future studies, especially in urooncology, bearing in mind possible cardiotoxic effects.
Keywords :
Cytostatic/cytotoxic effect , sorafenib , Cardiotoxic effect , statins , Sunitinib
Journal title :
Cancer Letters
Journal title :
Cancer Letters